@article {1160, title = {New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.}, journal = {Nat Genet}, volume = {42}, year = {2010}, month = {2010 Feb}, pages = {105-16}, abstract = {

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

}, keywords = {Adolescent, Adult, Alleles, Blood Glucose, Child, Databases, Genetic, Diabetes Mellitus, Type 2, DNA Copy Number Variations, Fasting, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeostasis, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Reproducibility of Results}, issn = {1546-1718}, doi = {10.1038/ng.520}, author = {Dupuis, Jos{\'e}e and Langenberg, Claudia and Prokopenko, Inga and Saxena, Richa and Soranzo, Nicole and Jackson, Anne U and Wheeler, Eleanor and Glazer, Nicole L and Bouatia-Naji, Nabila and Gloyn, Anna L and Lindgren, Cecilia M and M{\"a}gi, Reedik and Morris, Andrew P and Randall, Joshua and Johnson, Toby and Elliott, Paul and Rybin, Denis and Thorleifsson, Gudmar and Steinthorsdottir, Valgerdur and Henneman, Peter and Grallert, Harald and Dehghan, Abbas and Hottenga, Jouke Jan and Franklin, Christopher S and Navarro, Pau and Song, Kijoung and Goel, Anuj and Perry, John R B and Egan, Josephine M and Lajunen, Taina and Grarup, Niels and Spars{\o}, Thomas and Doney, Alex and Voight, Benjamin F and Stringham, Heather M and Li, Man and Kanoni, Stavroula and Shrader, Peter and Cavalcanti-Proen{\c c}a, Christine and Kumari, Meena and Qi, Lu and Timpson, Nicholas J and Gieger, Christian and Zabena, Carina and Rocheleau, Ghislain and Ingelsson, Erik and An, Ping and O{\textquoteright}Connell, Jeffrey and Luan, Jian{\textquoteright}an and Elliott, Amanda and McCarroll, Steven A and Payne, Felicity and Roccasecca, Rosa Maria and Pattou, Fran{\c c}ois and Sethupathy, Praveen and Ardlie, Kristin and Ariyurek, Yavuz and Balkau, Beverley and Barter, Philip and Beilby, John P and Ben-Shlomo, Yoav and Benediktsson, Rafn and Bennett, Amanda J and Bergmann, Sven and Bochud, Murielle and Boerwinkle, Eric and Bonnefond, Am{\'e}lie and Bonnycastle, Lori L and Borch-Johnsen, Knut and B{\"o}ttcher, Yvonne and Brunner, Eric and Bumpstead, Suzannah J and Charpentier, Guillaume and Chen, Yii-Der Ida and Chines, Peter and Clarke, Robert and Coin, Lachlan J M and Cooper, Matthew N and Cornelis, Marilyn and Crawford, Gabe and Crisponi, Laura and Day, Ian N M and de Geus, Eco J C and Delplanque, Jerome and Dina, Christian and Erdos, Michael R and Fedson, Annette C and Fischer-Rosinsky, Antje and Forouhi, Nita G and Fox, Caroline S and Frants, Rune and Franzosi, Maria Grazia and Galan, Pilar and Goodarzi, Mark O and Graessler, J{\"u}rgen and Groves, Christopher J and Grundy, Scott and Gwilliam, Rhian and Gyllensten, Ulf and Hadjadj, Samy and Hallmans, G{\"o}ran and Hammond, Naomi and Han, Xijing and Hartikainen, Anna-Liisa and Hassanali, Neelam and Hayward, Caroline and Heath, Simon C and Hercberg, Serge and Herder, Christian and Hicks, Andrew A and Hillman, David R and Hingorani, Aroon D and Hofman, Albert and Hui, Jennie and Hung, Joe and Isomaa, Bo and Johnson, Paul R V and J{\o}rgensen, Torben and Jula, Antti and Kaakinen, Marika and Kaprio, Jaakko and Kesaniemi, Y Antero and Kivimaki, Mika and Knight, Beatrice and Koskinen, Seppo and Kovacs, Peter and Kyvik, Kirsten Ohm and Lathrop, G Mark and Lawlor, Debbie A and Le Bacquer, Olivier and Lecoeur, C{\'e}cile and Li, Yun and Lyssenko, Valeriya and Mahley, Robert and Mangino, Massimo and Manning, Alisa K and Mart{\'\i}nez-Larrad, Mar{\'\i}a Teresa and McAteer, Jarred B and McCulloch, Laura J and McPherson, Ruth and Meisinger, Christa and Melzer, David and Meyre, David and Mitchell, Braxton D and Morken, Mario A and Mukherjee, Sutapa and Naitza, Silvia and Narisu, Narisu and Neville, Matthew J and Oostra, Ben A and Orr{\`u}, Marco and Pakyz, Ruth and Palmer, Colin N A and Paolisso, Giuseppe and Pattaro, Cristian and Pearson, Daniel and Peden, John F and Pedersen, Nancy L and Perola, Markus and Pfeiffer, Andreas F H and Pichler, Irene and Polasek, Ozren and Posthuma, Danielle and Potter, Simon C and Pouta, Anneli and Province, Michael A and Psaty, Bruce M and Rathmann, Wolfgang and Rayner, Nigel W and Rice, Kenneth and Ripatti, Samuli and Rivadeneira, Fernando and Roden, Michael and Rolandsson, Olov and Sandbaek, Annelli and Sandhu, Manjinder and Sanna, Serena and Sayer, Avan Aihie and Scheet, Paul and Scott, Laura J and Seedorf, Udo and Sharp, Stephen J and Shields, Beverley and Sigurethsson, Gunnar and Sijbrands, Eric J G and Silveira, Angela and Simpson, Laila and Singleton, Andrew and Smith, Nicholas L and Sovio, Ulla and Swift, Amy and Syddall, Holly and Syv{\"a}nen, Ann-Christine and Tanaka, Toshiko and Thorand, Barbara and Tichet, Jean and T{\"o}njes, Anke and Tuomi, Tiinamaija and Uitterlinden, Andr{\'e} G and van Dijk, Ko Willems and van Hoek, Mandy and Varma, Dhiraj and Visvikis-Siest, Sophie and Vitart, Veronique and Vogelzangs, Nicole and Waeber, G{\'e}rard and Wagner, Peter J and Walley, Andrew and Walters, G Bragi and Ward, Kim L and Watkins, Hugh and Weedon, Michael N and Wild, Sarah H and Willemsen, Gonneke and Witteman, Jaqueline C M and Yarnell, John W G and Zeggini, Eleftheria and Zelenika, Diana and Zethelius, Bj{\"o}rn and Zhai, Guangju and Zhao, Jing Hua and Zillikens, M Carola and Borecki, Ingrid B and Loos, Ruth J F and Meneton, Pierre and Magnusson, Patrik K E and Nathan, David M and Williams, Gordon H and Hattersley, Andrew T and Silander, Kaisa and Salomaa, Veikko and Smith, George Davey and Bornstein, Stefan R and Schwarz, Peter and Spranger, Joachim and Karpe, Fredrik and Shuldiner, Alan R and Cooper, Cyrus and Dedoussis, George V and Serrano-R{\'\i}os, Manuel and Morris, Andrew D and Lind, Lars and Palmer, Lyle J and Hu, Frank B and Franks, Paul W and Ebrahim, Shah and Marmot, Michael and Kao, W H Linda and Pankow, James S and Sampson, Michael J and Kuusisto, Johanna and Laakso, Markku and Hansen, Torben and Pedersen, Oluf and Pramstaller, Peter Paul and Wichmann, H Erich and Illig, Thomas and Rudan, Igor and Wright, Alan F and Stumvoll, Michael and Campbell, Harry and Wilson, James F and Bergman, Richard N and Buchanan, Thomas A and Collins, Francis S and Mohlke, Karen L and Tuomilehto, Jaakko and Valle, Timo T and Altshuler, David and Rotter, Jerome I and Siscovick, David S and Penninx, Brenda W J H and Boomsma, Dorret I and Deloukas, Panos and Spector, Timothy D and Frayling, Timothy M and Ferrucci, Luigi and Kong, Augustine and Thorsteinsdottir, Unnur and Stefansson, Kari and van Duijn, Cornelia M and Aulchenko, Yurii S and Cao, Antonio and Scuteri, Angelo and Schlessinger, David and Uda, Manuela and Ruokonen, Aimo and Jarvelin, Marjo-Riitta and Waterworth, Dawn M and Vollenweider, Peter and Peltonen, Leena and Mooser, Vincent and Abecasis, Goncalo R and Wareham, Nicholas J and Sladek, Robert and Froguel, Philippe and Watanabe, Richard M and Meigs, James B and Groop, Leif and Boehnke, Michael and McCarthy, Mark I and Florez, Jose C and Barroso, In{\^e}s} } @article {1378, title = {Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.}, journal = {PLoS Genet}, volume = {8}, year = {2012}, month = {2012}, pages = {e1002607}, abstract = {

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5{\texttimes}10(-8)-1.2{\texttimes}10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3{\texttimes}10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3{\texttimes}10(-3), n = 22,044), increased triglycerides (p = 2.6{\texttimes}10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8{\texttimes}10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4{\texttimes}10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5{\texttimes}10(-13), n = 96,748) and decreased BMI (p = 1.4{\texttimes}10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

}, keywords = {Adiponectin, African Americans, Asian Continental Ancestry Group, Cholesterol, HDL, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002607}, author = {Dastani, Zari and Hivert, Marie-France and Timpson, Nicholas and Perry, John R B and Yuan, Xin and Scott, Robert A and Henneman, Peter and Heid, Iris M and Kizer, Jorge R and Lyytik{\"a}inen, Leo-Pekka and Fuchsberger, Christian and Tanaka, Toshiko and Morris, Andrew P and Small, Kerrin and Isaacs, Aaron and Beekman, Marian and Coassin, Stefan and Lohman, Kurt and Qi, Lu and Kanoni, Stavroula and Pankow, James S and Uh, Hae-Won and Wu, Ying and Bidulescu, Aurelian and Rasmussen-Torvik, Laura J and Greenwood, Celia M T and Ladouceur, Martin and Grimsby, Jonna and Manning, Alisa K and Liu, Ching-Ti and Kooner, Jaspal and Mooser, Vincent E and Vollenweider, Peter and Kapur, Karen A and Chambers, John and Wareham, Nicholas J and Langenberg, Claudia and Frants, Rune and Willems-Vandijk, Ko and Oostra, Ben A and Willems, Sara M and Lamina, Claudia and Winkler, Thomas W and Psaty, Bruce M and Tracy, Russell P and Brody, Jennifer and Chen, Ida and Viikari, Jorma and K{\"a}h{\"o}nen, Mika and Pramstaller, Peter P and Evans, David M and St Pourcain, Beate and Sattar, Naveed and Wood, Andrew R and Bandinelli, Stefania and Carlson, Olga D and Egan, Josephine M and B{\"o}hringer, Stefan and van Heemst, Diana and Kedenko, Lyudmyla and Kristiansson, Kati and Nuotio, Marja-Liisa and Loo, Britt-Marie and Harris, Tamara and Garcia, Melissa and Kanaya, Alka and Haun, Margot and Klopp, Norman and Wichmann, H-Erich and Deloukas, Panos and Katsareli, Efi and Couper, David J and Duncan, Bruce B and Kloppenburg, Margreet and Adair, Linda S and Borja, Judith B and Wilson, James G and Musani, Solomon and Guo, Xiuqing and Johnson, Toby and Semple, Robert and Teslovich, Tanya M and Allison, Matthew A and Redline, Susan and Buxbaum, Sarah G and Mohlke, Karen L and Meulenbelt, Ingrid and Ballantyne, Christie M and Dedoussis, George V and Hu, Frank B and Liu, Yongmei and Paulweber, Bernhard and Spector, Timothy D and Slagboom, P Eline and Ferrucci, Luigi and Jula, Antti and Perola, Markus and Raitakari, Olli and Florez, Jose C and Salomaa, Veikko and Eriksson, Johan G and Frayling, Timothy M and Hicks, Andrew A and Lehtim{\"a}ki, Terho and Smith, George Davey and Siscovick, David S and Kronenberg, Florian and van Duijn, Cornelia and Loos, Ruth J F and Waterworth, Dawn M and Meigs, James B and Dupuis, Jos{\'e}e and Richards, J Brent and Voight, Benjamin F and Scott, Laura J and Steinthorsdottir, Valgerdur and Dina, Christian and Welch, Ryan P and Zeggini, Eleftheria and Huth, Cornelia and Aulchenko, Yurii S and Thorleifsson, Gudmar and McCulloch, Laura J and Ferreira, Teresa and Grallert, Harald and Amin, Najaf and Wu, Guanming and Willer, Cristen J and Raychaudhuri, Soumya and McCarroll, Steve A and Hofmann, Oliver M and Segr{\`e}, Ayellet V and van Hoek, Mandy and Navarro, Pau and Ardlie, Kristin and Balkau, Beverley and Benediktsson, Rafn and Bennett, Amanda J and Blagieva, Roza and Boerwinkle, Eric and Bonnycastle, Lori L and Bostr{\"o}m, Kristina Bengtsson and Bravenboer, Bert and Bumpstead, Suzannah and Burtt, Noel P and Charpentier, Guillaume and Chines, Peter S and Cornelis, Marilyn and Crawford, Gabe and Doney, Alex S F and Elliott, Katherine S and Elliott, Amanda L and Erdos, Michael R and Fox, Caroline S and Franklin, Christopher S and Ganser, Martha and Gieger, Christian and Grarup, Niels and Green, Todd and Griffin, Simon and Groves, Christopher J and Guiducci, Candace and Hadjadj, Samy and Hassanali, Neelam and Herder, Christian and Isomaa, Bo and Jackson, Anne U and Johnson, Paul R V and J{\o}rgensen, Torben and Kao, Wen H L and Kong, Augustine and Kraft, Peter and Kuusisto, Johanna and Lauritzen, Torsten and Li, Man and Lieverse, Aloysius and Lindgren, Cecilia M and Lyssenko, Valeriya and Marre, Michel and Meitinger, Thomas and Midthjell, Kristian and Morken, Mario A and Narisu, Narisu and Nilsson, Peter and Owen, Katharine R and Payne, Felicity and Petersen, Ann-Kristin and Platou, Carl and Proen{\c c}a, Christine and Prokopenko, Inga and Rathmann, Wolfgang and Rayner, N William and Robertson, Neil R and Rocheleau, Ghislain and Roden, Michael and Sampson, Michael J and Saxena, Richa and Shields, Beverley M and Shrader, Peter and Sigurdsson, Gunnar and Spars{\o}, Thomas and Strassburger, Klaus and Stringham, Heather M and Sun, Qi and Swift, Amy J and Thorand, Barbara and Tichet, Jean and Tuomi, Tiinamaija and van Dam, Rob M and van Haeften, Timon W and van Herpt, Thijs and van Vliet-Ostaptchouk, Jana V and Walters, G Bragi and Weedon, Michael N and Wijmenga, Cisca and Witteman, Jacqueline and Bergman, Richard N and Cauchi, Stephane and Collins, Francis S and Gloyn, Anna L and Gyllensten, Ulf and Hansen, Torben and Hide, Winston A and Hitman, Graham A and Hofman, Albert and Hunter, David J and Hveem, Kristian and Laakso, Markku and Morris, Andrew D and Palmer, Colin N A and Rudan, Igor and Sijbrands, Eric and Stein, Lincoln D and Tuomilehto, Jaakko and Uitterlinden, Andre and Walker, Mark and Watanabe, Richard M and Abecasis, Goncalo R and Boehm, Bernhard O and Campbell, Harry and Daly, Mark J and Hattersley, Andrew T and Pedersen, Oluf and Barroso, In{\^e}s and Groop, Leif and Sladek, Rob and Thorsteinsdottir, Unnur and Wilson, James F and Illig, Thomas and Froguel, Philippe and van Duijn, Cornelia M and Stefansson, Kari and Altshuler, David and Boehnke, Michael and McCarthy, Mark I and Soranzo, Nicole and Wheeler, Eleanor and Glazer, Nicole L and Bouatia-Naji, Nabila and M{\"a}gi, Reedik and Randall, Joshua and Elliott, Paul and Rybin, Denis and Dehghan, Abbas and Hottenga, Jouke Jan and Song, Kijoung and Goel, Anuj and Lajunen, Taina and Doney, Alex and Cavalcanti-Proen{\c c}a, Christine and Kumari, Meena and Timpson, Nicholas J and Zabena, Carina and Ingelsson, Erik and An, Ping and O{\textquoteright}Connell, Jeffrey and Luan, Jian{\textquoteright}an and Elliott, Amanda and McCarroll, Steven A and Roccasecca, Rosa Maria and Pattou, Fran{\c c}ois and Sethupathy, Praveen and Ariyurek, Yavuz and Barter, Philip and Beilby, John P and Ben-Shlomo, Yoav and Bergmann, Sven and Bochud, Murielle and Bonnefond, Am{\'e}lie and Borch-Johnsen, Knut and B{\"o}ttcher, Yvonne and Brunner, Eric and Bumpstead, Suzannah J and Chen, Yii-Der Ida and Chines, Peter and Clarke, Robert and Coin, Lachlan J M and Cooper, Matthew N and Crisponi, Laura and Day, Ian N M and de Geus, Eco J C and Delplanque, Jerome and Fedson, Annette C and Fischer-Rosinsky, Antje and Forouhi, Nita G and Franzosi, Maria Grazia and Galan, Pilar and Goodarzi, Mark O and Graessler, J{\"u}rgen and Grundy, Scott and Gwilliam, Rhian and Hallmans, G{\"o}ran and Hammond, Naomi and Han, Xijing and Hartikainen, Anna-Liisa and Hayward, Caroline and Heath, Simon C and Hercberg, Serge and Hillman, David R and Hingorani, Aroon D and Hui, Jennie and Hung, Joe and Kaakinen, Marika and Kaprio, Jaakko and Kesaniemi, Y Antero and Kivimaki, Mika and Knight, Beatrice and Koskinen, Seppo and Kovacs, Peter and Kyvik, Kirsten Ohm and Lathrop, G Mark and Lawlor, Debbie A and Le Bacquer, Olivier and Lecoeur, C{\'e}cile and Li, Yun and Mahley, Robert and Mangino, Massimo and Mart{\'\i}nez-Larrad, Mar{\'\i}a Teresa and McAteer, Jarred B and McPherson, Ruth and Meisinger, Christa and Melzer, David and Meyre, David and Mitchell, Braxton D and Mukherjee, Sutapa and Naitza, Silvia and Neville, Matthew J and Orr{\`u}, Marco and Pakyz, Ruth and Paolisso, Giuseppe and Pattaro, Cristian and Pearson, Daniel and Peden, John F and Pedersen, Nancy L and Pfeiffer, Andreas F H and Pichler, Irene and Polasek, Ozren and Posthuma, Danielle and Potter, Simon C and Pouta, Anneli and Province, Michael A and Rayner, Nigel W and Rice, Kenneth and Ripatti, Samuli and Rivadeneira, Fernando and Rolandsson, Olov and Sandbaek, Annelli and Sandhu, Manjinder and Sanna, Serena and Sayer, Avan Aihie and Scheet, Paul and Seedorf, Udo and Sharp, Stephen J and Shields, Beverley and Sigur{\dh}sson, Gunnar and Sijbrands, Eric J G and Silveira, Angela and Simpson, Laila and Singleton, Andrew and Smith, Nicholas L and Sovio, Ulla and Swift, Amy and Syddall, Holly and Syv{\"a}nen, Ann-Christine and T{\"o}njes, Anke and Uitterlinden, Andr{\'e} G and van Dijk, Ko Willems and Varma, Dhiraj and Visvikis-Siest, Sophie and Vitart, Veronique and Vogelzangs, Nicole and Waeber, G{\'e}rard and Wagner, Peter J and Walley, Andrew and Ward, Kim L and Watkins, Hugh and Wild, Sarah H and Willemsen, Gonneke and Witteman, Jaqueline C M and Yarnell, John W G and Zelenika, Diana and Zethelius, Bj{\"o}rn and Zhai, Guangju and Zhao, Jing Hua and Zillikens, M Carola and Borecki, Ingrid B and Meneton, Pierre and Magnusson, Patrik K E and Nathan, David M and Williams, Gordon H and Silander, Kaisa and Bornstein, Stefan R and Schwarz, Peter and Spranger, Joachim and Karpe, Fredrik and Shuldiner, Alan R and Cooper, Cyrus and Serrano-R{\'\i}os, Manuel and Lind, Lars and Palmer, Lyle J and Hu, Frank B and Franks, Paul W and Ebrahim, Shah and Marmot, Michael and Kao, W H Linda and Pramstaller, Peter Paul and Wright, Alan F and Stumvoll, Michael and Hamsten, Anders and Buchanan, Thomas A and Valle, Timo T and Rotter, Jerome I and Penninx, Brenda W J H and Boomsma, Dorret I and Cao, Antonio and Scuteri, Angelo and Schlessinger, David and Uda, Manuela and Ruokonen, Aimo and Jarvelin, Marjo-Riitta and Peltonen, Leena and Mooser, Vincent and Sladek, Robert and Musunuru, Kiran and Smith, Albert V and Edmondson, Andrew C and Stylianou, Ioannis M and Koseki, Masahiro and Pirruccello, James P and Chasman, Daniel I and Johansen, Christopher T and Fouchier, Sigrid W and Peloso, Gina M and Barbalic, Maja and Ricketts, Sally L and Bis, Joshua C and Feitosa, Mary F and Orho-Melander, Marju and Melander, Olle and Li, Xiaohui and Li, Mingyao and Cho, Yoon Shin and Go, Min Jin and Kim, Young Jin and Lee, Jong-Young and Park, Taesung and Kim, Kyunga and Sim, Xueling and Ong, Rick Twee-Hee and Croteau-Chonka, Damien C and Lange, Leslie A and Smith, Joshua D and Ziegler, Andreas and Zhang, Weihua and Zee, Robert Y L and Whitfield, John B and Thompson, John R and Surakka, Ida and Spector, Tim D and Smit, Johannes H and Sinisalo, Juha and Scott, James and Saharinen, Juha and Sabatti, Chiara and Rose, Lynda M and Roberts, Robert and Rieder, Mark and Parker, Alex N and Par{\'e}, Guillaume and O{\textquoteright}Donnell, Christopher J and Nieminen, Markku S and Nickerson, Deborah A and Montgomery, Grant W and McArdle, Wendy and Masson, David and Martin, Nicholas G and Marroni, Fabio and Lucas, Gavin and Luben, Robert and Lokki, Marja-Liisa and Lettre, Guillaume and Launer, Lenore J and Lakatta, Edward G and Laaksonen, Reijo and Kyvik, Kirsten O and K{\"o}nig, Inke R and Khaw, Kay-Tee and Kaplan, Lee M and Johansson, Asa and Janssens, A Cecile J W and Igl, Wilmar and Hovingh, G Kees and Hengstenberg, Christian and Havulinna, Aki S and Hastie, Nicholas D and Harris, Tamara B and Haritunians, Talin and Hall, Alistair S and Groop, Leif C and Gonzalez, Elena and Freimer, Nelson B and Erdmann, Jeanette and Ejebe, Kenechi G and D{\"o}ring, Angela and Dominiczak, Anna F and Demissie, Serkalem and Deloukas, Panagiotis and de Faire, Ulf and Crawford, Gabriel and Chen, Yii-der I and Caulfield, Mark J and Boekholdt, S Matthijs and Assimes, Themistocles L and Quertermous, Thomas and Seielstad, Mark and Wong, Tien Y and Tai, E-Shyong and Feranil, Alan B and Kuzawa, Christopher W and Taylor, Herman A and Gabriel, Stacey B and Holm, Hilma and Gudnason, Vilmundur and Krauss, Ronald M and Ordovas, Jose M and Munroe, Patricia B and Kooner, Jaspal S and Tall, Alan R and Hegele, Robert A and Kastelein, John J P and Schadt, Eric E and Strachan, David P and Reilly, Muredach P and Samani, Nilesh J and Schunkert, Heribert and Cupples, L Adrienne and Sandhu, Manjinder S and Ridker, Paul M and Rader, Daniel J and Kathiresan, Sekar} } @article {8198, title = {Associations of autozygosity with a broad range of human phenotypes.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 Oct 31}, pages = {4957}, abstract = {

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55\% decrease [95\% CI 44-66\%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-12283-6}, author = {Clark, David W and Okada, Yukinori and Moore, Kristjan H S and Mason, Dan and Pirastu, Nicola and Gandin, Ilaria and Mattsson, Hannele and Barnes, Catriona L K and Lin, Kuang and Zhao, Jing Hua and Deelen, Patrick and Rohde, Rebecca and Schurmann, Claudia and Guo, Xiuqing and Giulianini, Franco and Zhang, Weihua and Medina-G{\'o}mez, Carolina and Karlsson, Robert and Bao, Yanchun and Bartz, Traci M and Baumbach, Clemens and Biino, Ginevra and Bixley, Matthew J and Brumat, Marco and Chai, Jin-Fang and Corre, Tanguy and Cousminer, Diana L and Dekker, Annelot M and Eccles, David A and van Eijk, Kristel R and Fuchsberger, Christian and Gao, He and Germain, Marine and Gordon, Scott D and de Haan, Hugoline G and Harris, Sarah E and Hofer, Edith and Huerta-Chagoya, Alicia and Igartua, Catherine and Jansen, Iris E and Jia, Yucheng and Kacprowski, Tim and Karlsson, Torgny and Kleber, Marcus E and Li, Shengchao Alfred and Li-Gao, Ruifang and Mahajan, Anubha and Matsuda, Koichi and Meidtner, Karina and Meng, Weihua and Montasser, May E and van der Most, Peter J and Munz, Matthias and Nutile, Teresa and Palviainen, Teemu and Prasad, Gauri and Prasad, Rashmi B and Priyanka, Tallapragada Divya Sri and Rizzi, Federica and Salvi, Erika and Sapkota, Bishwa R and Shriner, Daniel and Skotte, Line and Smart, Melissa C and Smith, Albert Vernon and van der Spek, Ashley and Spracklen, Cassandra N and Strawbridge, Rona J and Tajuddin, Salman M and Trompet, Stella and Turman, Constance and Verweij, Niek and Viberti, Clara and Wang, Lihua and Warren, Helen R and Wootton, Robyn E and Yanek, Lisa R and Yao, Jie and Yousri, Noha A and Zhao, Wei and Adeyemo, Adebowale A and Afaq, Saima and Aguilar-Salinas, Carlos Alberto and Akiyama, Masato and Albert, Matthew L and Allison, Matthew A and Alver, Maris and Aung, Tin and Azizi, Fereidoun and Bentley, Amy R and Boeing, Heiner and Boerwinkle, Eric and Borja, Judith B and de Borst, Gert J and Bottinger, Erwin P and Broer, Linda and Campbell, Harry and Chanock, Stephen and Chee, Miao-Li and Chen, Guanjie and Chen, Yii-der I and Chen, Zhengming and Chiu, Yen-Feng and Cocca, Massimiliano and Collins, Francis S and Concas, Maria Pina and Corley, Janie and Cugliari, Giovanni and van Dam, Rob M and Damulina, Anna and Daneshpour, Maryam S and Day, Felix R and Delgado, Graciela E and Dhana, Klodian and Doney, Alexander S F and D{\"o}rr, Marcus and Doumatey, Ayo P and Dzimiri, Nduna and Ebenesersd{\'o}ttir, S Sunna and Elliott, Joshua and Elliott, Paul and Ewert, Ralf and Felix, Janine F and Fischer, Krista and Freedman, Barry I and Girotto, Giorgia and Goel, Anuj and G{\"o}gele, Martin and Goodarzi, Mark O and Graff, Mariaelisa and Granot-Hershkovitz, Einat and Grodstein, Francine and Guarrera, Simonetta and Gudbjartsson, Daniel F and Guity, Kamran and Gunnarsson, Bjarni and Guo, Yu and Hagenaars, Saskia P and Haiman, Christopher A and Halevy, Avner and Harris, Tamara B and Hedayati, Mehdi and van Heel, David A and Hirata, Makoto and H{\"o}fer, Imo and Hsiung, Chao Agnes and Huang, Jinyan and Hung, Yi-Jen and Ikram, M Arfan and Jagadeesan, Anuradha and Jousilahti, Pekka and Kamatani, Yoichiro and Kanai, Masahiro and Kerrison, Nicola D and Kessler, Thorsten and Khaw, Kay-Tee and Khor, Chiea Chuen and de Kleijn, Dominique P V and Koh, Woon-Puay and Kolcic, Ivana and Kraft, Peter and Kr{\"a}mer, Bernhard K and Kutalik, Zolt{\'a}n and Kuusisto, Johanna and Langenberg, Claudia and Launer, Lenore J and Lawlor, Deborah A and Lee, I-Te and Lee, Wen-Jane and Lerch, Markus M and Li, Liming and Liu, Jianjun and Loh, Marie and London, Stephanie J and Loomis, Stephanie and Lu, Yingchang and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Manichaikul, Ani W and Manunta, Paolo and M{\'a}sson, G{\'\i}sli and Matoba, Nana and Mei, Xue W and Meisinger, Christa and Meitinger, Thomas and Mezzavilla, Massimo and Milani, Lili and Millwood, Iona Y and Momozawa, Yukihide and Moore, Amy and Morange, Pierre-Emmanuel and Moreno-Macias, Hortensia and Mori, Trevor A and Morrison, Alanna C and Muka, Taulant and Murakami, Yoshinori and Murray, Alison D and de Mutsert, Ren{\'e}e and Mychaleckyj, Josyf C and Nalls, Mike A and Nauck, Matthias and Neville, Matt J and Nolte, Ilja M and Ong, Ken K and Orozco, Lorena and Padmanabhan, Sandosh and P{\'a}lsson, Gunnar and Pankow, James S and Pattaro, Cristian and Pattie, Alison and Polasek, Ozren and Poulter, Neil and Pramstaller, Peter P and Quintana-Murci, Lluis and R{\"a}ikk{\"o}nen, Katri and Ralhan, Sarju and Rao, Dabeeru C and van Rheenen, Wouter and Rich, Stephen S and Ridker, Paul M and Rietveld, Cornelius A and Robino, Antonietta and van Rooij, Frank J A and Ruggiero, Daniela and Saba, Yasaman and Sabanayagam, Charumathi and Sabater-Lleal, Maria and Sala, Cinzia Felicita and Salomaa, Veikko and Sandow, Kevin and Schmidt, Helena and Scott, Laura J and Scott, William R and Sedaghati-Khayat, Bahareh and Sennblad, Bengt and van Setten, Jessica and Sever, Peter J and Sheu, Wayne H-H and Shi, Yuan and Shrestha, Smeeta and Shukla, Sharvari Rahul and Sigurdsson, Jon K and Sikka, Timo Tonis and Singh, Jai Rup and Smith, Blair H and Stan{\v c}{\'a}kov{\'a}, Alena and Stanton, Alice and Starr, John M and Stefansdottir, Lilja and Straker, Leon and Sulem, Patrick and Sveinbjornsson, Gardar and Swertz, Morris A and Taylor, Adele M and Taylor, Kent D and Terzikhan, Natalie and Tham, Yih-Chung and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Tillander, Annika and Tracy, Russell P and Tusi{\'e}-Luna, Teresa and Tzoulaki, Ioanna and Vaccargiu, Simona and Vangipurapu, Jagadish and Veldink, Jan H and Vitart, Veronique and V{\"o}lker, Uwe and Vuoksimaa, Eero and Wakil, Salma M and Waldenberger, Melanie and Wander, Gurpreet S and Wang, Ya Xing and Wareham, Nicholas J and Wild, Sarah and Yajnik, Chittaranjan S and Yuan, Jian-Min and Zeng, Lingyao and Zhang, Liang and Zhou, Jie and Amin, Najaf and Asselbergs, Folkert W and Bakker, Stephan J L and Becker, Diane M and Lehne, Benjamin and Bennett, David A and van den Berg, Leonard H and Berndt, Sonja I and Bharadwaj, Dwaipayan and Bielak, Lawrence F and Bochud, Murielle and Boehnke, Mike and Bouchard, Claude and Bradfield, Jonathan P and Brody, Jennifer A and Campbell, Archie and Carmi, Shai and Caulfield, Mark J and Cesarini, David and Chambers, John C and Chandak, Giriraj Ratan and Cheng, Ching-Yu and Ciullo, Marina and Cornelis, Marilyn and Cusi, Daniele and Smith, George Davey and Deary, Ian J and Dorajoo, Rajkumar and van Duijn, Cornelia M and Ellinghaus, David and Erdmann, Jeanette and Eriksson, Johan G and Evangelou, Evangelos and Evans, Michele K and Faul, Jessica D and Feenstra, Bjarke and Feitosa, Mary and Foisy, Sylvain and Franke, Andre and Friedlander, Yechiel and Gasparini, Paolo and Gieger, Christian and Gonzalez, Clicerio and Goyette, Philippe and Grant, Struan F A and Griffiths, Lyn R and Groop, Leif and Gudnason, Vilmundur and Gyllensten, Ulf and Hakonarson, Hakon and Hamsten, Anders and van der Harst, Pim and Heng, Chew-Kiat and Hicks, Andrew A and Hochner, Hagit and Huikuri, Heikki and Hunt, Steven C and Jaddoe, Vincent W V and De Jager, Philip L and Johannesson, Magnus and Johansson, Asa and Jonas, Jost B and Jukema, J Wouter and Junttila, Juhani and Kaprio, Jaakko and Kardia, Sharon L R and Karpe, Fredrik and Kumari, Meena and Laakso, Markku and van der Laan, Sander W and Lahti, Jari and Laudes, Matthias and Lea, Rodney A and Lieb, Wolfgang and Lumley, Thomas and Martin, Nicholas G and M{\"a}rz, Winfried and Matullo, Giuseppe and McCarthy, Mark I and Medland, Sarah E and Merriman, Tony R and Metspalu, Andres and Meyer, Brian F and Mohlke, Karen L and Montgomery, Grant W and Mook-Kanamori, Dennis and Munroe, Patricia B and North, Kari E and Nyholt, Dale R and O{\textquoteright}Connell, Jeffery R and Ober, Carole and Oldehinkel, Albertine J and Palmas, Walter and Palmer, Colin and Pasterkamp, Gerard G and Patin, Etienne and Pennell, Craig E and Perusse, Louis and Peyser, Patricia A and Pirastu, Mario and Polderman, Tinca J C and Porteous, David J and Posthuma, Danielle and Psaty, Bruce M and Rioux, John D and Rivadeneira, Fernando and Rotimi, Charles and Rotter, Jerome I and Rudan, Igor and den Ruijter, Hester M and Sanghera, Dharambir K and Sattar, Naveed and Schmidt, Reinhold and Schulze, Matthias B and Schunkert, Heribert and Scott, Robert A and Shuldiner, Alan R and Sim, Xueling and Small, Neil and Smith, Jennifer A and Sotoodehnia, Nona and Tai, E-Shyong and Teumer, Alexander and Timpson, Nicholas J and Toniolo, Daniela and Tr{\'e}gou{\"e}t, David-Alexandre and Tuomi, Tiinamaija and Vollenweider, Peter and Wang, Carol A and Weir, David R and Whitfield, John B and Wijmenga, Cisca and Wong, Tien-Yin and Wright, John and Yang, Jingyun and Yu, Lei and Zemel, Babette S and Zonderman, Alan B and Perola, Markus and Magnusson, Patrik K E and Uitterlinden, Andr{\'e} G and Kooner, Jaspal S and Chasman, Daniel I and Loos, Ruth J F and Franceschini, Nora and Franke, Lude and Haley, Chris S and Hayward, Caroline and Walters, Robin G and Perry, John R B and Esko, T{\~o}nu and Helgason, Agnar and Stefansson, Kari and Joshi, Peter K and Kubo, Michiaki and Wilson, James F} } @article {8506, title = {The genetic architecture of the human cerebral cortex}, journal = {Science}, volume = {367}, year = {2020}, month = {Aug-03-2021}, pages = {eaay6690}, issn = {0036-8075}, doi = {10.1126/science.aay6690}, url = {https://www.sciencemag.org/lookup/doi/10.1126/science.aay6690https://syndication.highwire.org/content/doi/10.1126/science.aay6690https://syndication.highwire.org/content/doi/10.1126/science.aay6690}, author = {Grasby, Katrina L. and Jahanshad, Neda and Painter, Jodie N. and Colodro-Conde, Luc{\'\i}a and Bralten, Janita and Hibar, Derrek P. and Lind, Penelope A. and Pizzagalli, Fabrizio and Ching, Christopher R. K. and McMahon, Mary Agnes B. and Shatokhina, Natalia and Zsembik, Leo C. P. and Thomopoulos, Sophia I. and Zhu, Alyssa H. and Strike, Lachlan T. and Agartz, Ingrid and Alhusaini, Saud and Almeida, Marcio A. A. and Aln{\ae}s, Dag and Amlien, Inge K. and Andersson, Micael and Ard, Tyler and Armstrong, Nicola J. and Ashley-Koch, Allison and Atkins, Joshua R. and Bernard, Manon and Brouwer, Rachel M. and Buimer, Elizabeth E. L. and B{\"u}low, Robin and B{\"u}rger, Christian and Cannon, Dara M. and Chakravarty, Mallar and Chen, Qiang and Cheung, Joshua W. and Couvy-Duchesne, Baptiste and Dale, Anders M. and Dalvie, Shareefa and de Araujo, T{\^a}nia K. and de Zubicaray, Greig I. and de Zwarte, Sonja M. C. and den Braber, Anouk and Doan, Nhat Trung and Dohm, Katharina and Ehrlich, Stefan and Engelbrecht, Hannah-Ruth and Erk, Susanne and Fan, Chun Chieh and Fedko, Iryna O. and Foley, Sonya F. and Ford, Judith M. and Fukunaga, Masaki and Garrett, Melanie E. and Ge, Tian and Giddaluru, Sudheer and Goldman, Aaron L. and Green, Melissa J. and Groenewold, Nynke A. and Grotegerd, Dominik and Gurholt, Tiril P. and Gutman, Boris A. and Hansell, Narelle K. and Harris, Mathew A. and Harrison, Marc B. and Haswell, Courtney C. and Hauser, Michael and Herms, Stefan and Heslenfeld, Dirk J. and Ho, New Fei and Hoehn, David and Hoffmann, Per and Holleran, Laurena and Hoogman, Martine and Hottenga, Jouke-Jan and Ikeda, Masashi and Janowitz, Deborah and Jansen, Iris E. and Jia, Tianye and Jockwitz, Christiane and Kanai, Ryota and Karama, Sherif and Kasperaviciute, Dalia and Kaufmann, Tobias and Kelly, Sinead and Kikuchi, Masataka and Klein, Marieke and Knapp, Michael and Knodt, Annchen R. and Kr{\"a}mer, Bernd and Lam, Max and Lancaster, Thomas M. and Lee, Phil H. and Lett, Tristram A. and Lewis, Lindsay B. and Lopes-Cendes, Iscia and Luciano, Michelle and Macciardi, Fabio and Marquand, Andre F. and Mathias, Samuel R. and Melzer, Tracy R. and Milaneschi, Yuri and Mirza-Schreiber, Nazanin and Moreira, Jose C. V. and M{\"u}hleisen, Thomas W. and M{\"u}ller-Myhsok, Bertram and Najt, Pablo and Nakahara, Soichiro and Nho, Kwangsik and Olde Loohuis, Loes M. and Orfanos, Dimitri Papadopoulos and Pearson, John F. and Pitcher, Toni L. and P{\"u}tz, Benno and Quid{\'e}, Yann and Ragothaman, Anjanibhargavi and Rashid, Faisal M. and Reay, William R. and Redlich, Ronny and Reinbold, C{\'e}line S. and Repple, Jonathan and Richard, Genevi{\`e}ve and Riedel, Brandalyn C. and Risacher, Shannon L. and Rocha, Cristiane S. and Mota, Nina Roth and Salminen, Lauren and Saremi, Arvin and Saykin, Andrew J. and Schlag, Fenja and Schmaal, Lianne and Schofield, Peter R. and Secolin, Rodrigo and Shapland, Chin Yang and Shen, Li and Shin, Jean and Shumskaya, Elena and S{\o}nderby, Ida E. and Sprooten, Emma and Tansey, Katherine E. and Teumer, Alexander and Thalamuthu, Anbupalam and Tordesillas-Gutierrez, Diana and Turner, Jessica A. and Uhlmann, Anne and Vallerga, Costanza Ludovica and van der Meer, Dennis and van Donkelaar, Marjolein M. J. and van Eijk, Liza and van Erp, Theo G. M. and van Haren, Neeltje E. M. and van Rooij, Daan and van Tol, Marie-Jose and Veldink, Jan H. and Verhoef, Ellen and Walton, Esther and Wang, Mingyuan and Wang, Yunpeng and Wardlaw, Joanna M. and Wen, Wei and Westlye, Lars T. and Whelan, Christopher D. and Witt, Stephanie H. and Wittfeld, Katharina and Wolf, Christiane and Wolfers, Thomas and Wu, Jing Qin and Yasuda, Clarissa L. and Zaremba, Dario and Zhang, Zuo and Zwiers, Marcel P. and Artiges, Eric and Assareh, Amelia A. and Ayesa-Arriola, Rosa and Belger, Aysenil and Brandt, Christine L. and Brown, Gregory G. and Cichon, Sven and Curran, Joanne E. and Davies, Gareth E. and Degenhardt, Franziska and Dennis, Michelle F. and Dietsche, Bruno and Djurovic, Srdjan and Doherty, Colin P. and Espiritu, Ryan and Garijo, Daniel and Gil, Yolanda and Gowland, Penny A. and Green, Robert C. and H{\"a}usler, Alexander N. and Heindel, Walter and Ho, Beng-Choon and Hoffmann, Wolfgang U. and Holsboer, Florian and Homuth, Georg and Hosten, Norbert and Jack, Clifford R. and Jang, MiHyun and Jansen, Andreas and Kimbrel, Nathan A. and Kolsk{\r a}r, Knut and Koops, Sanne and Krug, Axel and Lim, Kelvin O. and Luykx, Jurjen J. and Mathalon, Daniel H. and Mather, Karen A. and Mattay, Venkata S. and Matthews, Sarah and Mayoral Van Son, Jaqueline and McEwen, Sarah C. and Melle, Ingrid and Morris, Derek W. and Mueller, Bryon A. and Nauck, Matthias and Nordvik, Jan E. and N{\"o}then, Markus M. and O{\textquoteright}Leary, Daniel S. and Opel, Nils and Martinot, Marie-Laure Paill{\`e}re and Pike, G. Bruce and Preda, Adrian and Quinlan, Erin B. and Rasser, Paul E. and Ratnakar, Varun and Reppermund, Simone and Steen, Vidar M. and Tooney, Paul A. and Torres, F{\'a}bio R. and Veltman, Dick J. and Voyvodic, James T. and Whelan, Robert and White, Tonya and Yamamori, Hidenaga and Adams, Hieab H. H. and Bis, Joshua C. and Debette, Stephanie and DeCarli, Charles and Fornage, Myriam and Gudnason, Vilmundur and Hofer, Edith and Ikram, M. Arfan and Launer, Lenore and Longstreth, W. T. and Lopez, Oscar L. and Mazoyer, Bernard and Mosley, Thomas H. and Roshchupkin, Gennady V. and Satizabal, Claudia L. and Schmidt, Reinhold and Seshadri, Sudha and Yang, Qiong and Alvim, Marina K. M. and Ames, David and Anderson, Tim J. and Andreassen, Ole A. and Arias-Vasquez, Alejandro and Bastin, Mark E. and Baune, Bernhard T. and Beckham, Jean C. and Blangero, John and Boomsma, Dorret I. and Brodaty, Henry and Brunner, Han G. and Buckner, Randy L. and Buitelaar, Jan K. and Bustillo, Juan R. and Cahn, Wiepke and Cairns, Murray J. and Calhoun, Vince and Carr, Vaughan J. and Caseras, Xavier and Caspers, Svenja and Cavalleri, Gianpiero L. and Cendes, Fernando and Corvin, Aiden and Crespo-Facorro, Benedicto and Dalrymple-Alford, John C. and Dannlowski, Udo and de Geus, Eco J. C. and Deary, Ian J. and Delanty, Norman and Depondt, Chantal and Desrivi{\`e}res, Sylvane and Donohoe, Gary and Espeseth, Thomas and Fern{\'a}ndez, Guill{\'e}n and Fisher, Simon E. and Flor, Herta and Forstner, Andreas J. and Francks, Clyde and Franke, Barbara and Glahn, David C. and Gollub, Randy L. and Grabe, Hans J. and Gruber, Oliver and H{\r a}berg, Asta K. and Hariri, Ahmad R. and Hartman, Catharina A. and Hashimoto, Ryota and Heinz, Andreas and Henskens, Frans A. and Hillegers, Manon H. J. and Hoekstra, Pieter J. and Holmes, Avram J. and Hong, L. Elliot and Hopkins, William D. and Hulshoff Pol, Hilleke E. and Jernigan, Terry L. and J{\"o}nsson, Erik G. and Kahn, Ren{\'e} S. and Kennedy, Martin A. and Kircher, Tilo T. J. and Kochunov, Peter and Kwok, John B. J. and Le Hellard, Stephanie and Loughland, Carmel M. and Martin, Nicholas G. and Martinot, Jean-Luc and McDonald, Colm and McMahon, Katie L. and Meyer-Lindenberg, Andreas and Michie, Patricia T. and Morey, Rajendra A. and Mowry, Bryan and Nyberg, Lars and Oosterlaan, Jaap and Ophoff, Roel A. and Pantelis, Christos and Paus, Tom{\'a}{\v s} and Pausova, Zdenka and Penninx, Brenda W. J. H. and Polderman, Tinca J. C. and Posthuma, Danielle and Rietschel, Marcella and Roffman, Joshua L. and Rowland, Laura M. and Sachdev, Perminder S. and S{\"a}mann, Philipp G. and Schall, Ulrich and Schumann, Gunter and Scott, Rodney J. and Sim, Kang and Sisodiya, Sanjay M. and Smoller, Jordan W. and Sommer, Iris E. and St Pourcain, Beate and Stein, Dan J. and Toga, Arthur W. and Trollor, Julian N. and Van der Wee, Nic J. A. and van {\textquoteright}t Ent, Dennis and V{\"o}lzke, Henry and Walter, Henrik and Weber, Bernd and Weinberger, Daniel R. and Wright, Margaret J. and Zhou, Juan and Stein, Jason L. and Thompson, Paul M. and Medland, Sarah E.} } @article {9035, title = {New insights into the genetic etiology of Alzheimer{\textquoteright}s disease and related dementias.}, journal = {Nat Genet}, volume = {54}, year = {2022}, month = {2022 Apr}, pages = {412-436}, abstract = {

Characterization of the genetic landscape of Alzheimer{\textquoteright}s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/{\textquoteright}proxy{\textquoteright} AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

}, keywords = {Alzheimer Disease, Cognitive Dysfunction, Genome-Wide Association Study, Humans, tau Proteins}, issn = {1546-1718}, doi = {10.1038/s41588-022-01024-z}, author = {Bellenguez, C{\'e}line and K{\"u}{\c c}{\"u}kali, Fahri and Jansen, Iris E and Kleineidam, Luca and Moreno-Grau, Sonia and Amin, Najaf and Naj, Adam C and Campos-Martin, Rafael and Grenier-Boley, Benjamin and Andrade, Victor and Holmans, Peter A and Boland, Anne and Damotte, Vincent and van der Lee, Sven J and Costa, Marcos R and Kuulasmaa, Teemu and Yang, Qiong and de Rojas, Itziar and Bis, Joshua C and Yaqub, Amber and Prokic, Ivana and Chapuis, Julien and Ahmad, Shahzad and Giedraitis, Vilmantas and Aarsland, Dag and Garcia-Gonzalez, Pablo and Abdelnour, Carla and Alarc{\'o}n-Mart{\'\i}n, Emilio and Alcolea, Daniel and Alegret, Montserrat and Alvarez, Ignacio and Alvarez, Victoria and Armstrong, Nicola J and Tsolaki, Anthoula and Antunez, Carmen and Appollonio, Ildebrando and Arcaro, Marina and Archetti, Silvana and Pastor, Alfonso Arias and Arosio, Beatrice and Athanasiu, Lavinia and Bailly, Henri and Banaj, Nerisa and Baquero, Miquel and Barral, Sandra and Beiser, Alexa and Pastor, Ana Bel{\'e}n and Below, Jennifer E and Benchek, Penelope and Benussi, Luisa and Berr, Claudine and Besse, C{\'e}line and Bessi, Valentina and Binetti, Giuliano and Bizarro, Alessandra and Blesa, Rafael and Boada, Merce and Boerwinkle, Eric and Borroni, Barbara and Boschi, Silvia and Boss{\`u}, Paola and Br{\r a}then, Geir and Bressler, Jan and Bresner, Catherine and Brodaty, Henry and Brookes, Keeley J and Brusco, Luis Ignacio and Buiza-Rueda, Dolores and B{\^u}rger, Katharina and Burholt, Vanessa and Bush, William S and Calero, Miguel and Cantwell, Laura B and Chene, Genevi{\`e}ve and Chung, Jaeyoon and Cuccaro, Michael L and Carracedo, Angel and Cecchetti, Roberta and Cervera-Carles, Laura and Charbonnier, Camille and Chen, Hung-Hsin and Chillotti, Caterina and Ciccone, Simona and Claassen, Jurgen A H R and Clark, Christopher and Conti, Elisa and Corma-G{\'o}mez, Ana{\"\i}s and Costantini, Emanuele and Custodero, Carlo and Daian, Delphine and Dalmasso, Maria Carolina and Daniele, Antonio and Dardiotis, Efthimios and Dartigues, Jean-Fran{\c c}ois and de Deyn, Peter Paul and de Paiva Lopes, Katia and de Witte, Lot D and Debette, Stephanie and Deckert, J{\"u}rgen and Del Ser, Teodoro and Denning, Nicola and DeStefano, Anita and Dichgans, Martin and Diehl-Schmid, Janine and Diez-Fairen, Monica and Rossi, Paolo Dionigi and Djurovic, Srdjan and Duron, Emmanuelle and D{\"u}zel, Emrah and Dufouil, Carole and Eiriksdottir, Gudny and Engelborghs, Sebastiaan and Escott-Price, Valentina and Espinosa, Ana and Ewers, Michael and Faber, Kelley M and Fabrizio, Tagliavini and Nielsen, Sune Fallgaard and Fardo, David W and Farotti, Lucia and Fenoglio, Chiara and Fern{\'a}ndez-Fuertes, Marta and Ferrari, Raffaele and Ferreira, Catarina B and Ferri, Evelyn and Fin, Bertrand and Fischer, Peter and Fladby, Tormod and Flie{\ss}bach, Klaus and Fongang, Bernard and Fornage, Myriam and Fortea, Juan and Foroud, Tatiana M and Fostinelli, Silvia and Fox, Nick C and Franco-Mac{\'\i}as, Emlio and Bullido, Mar{\'\i}a J and Frank-Garc{\'\i}a, Ana and Froelich, Lutz and Fulton-Howard, Brian and Galimberti, Daniela and Garc{\'\i}a-Alberca, Jose Maria and Garcia-Gonzalez, Pablo and Garcia-Madrona, Sebastian and Garcia-Ribas, Guillermo and Ghidoni, Roberta and Giegling, Ina and Giorgio, Giaccone and Goate, Alison M and Goldhardt, Oliver and Gomez-Fonseca, Duber and Gonz{\'a}lez-Perez, Antonio and Graff, Caroline and Grande, Giulia and Green, Emma and Grimmer, Timo and Gr{\"u}nblatt, Edna and Grunin, Michelle and Gudnason, Vilmundur and Guetta-Baranes, Tamar and Haapasalo, Annakaisa and Hadjigeorgiou, Georgios and Haines, Jonathan L and Hamilton-Nelson, Kara L and Hampel, Harald and Hanon, Olivier and Hardy, John and Hartmann, Annette M and Hausner, Lucrezia and Harwood, Janet and Heilmann-Heimbach, Stefanie and Helisalmi, Seppo and Heneka, Michael T and Hernandez, Isabel and Herrmann, Martin J and Hoffmann, Per and Holmes, Clive and Holstege, Henne and Vilas, Raquel Huerto and Hulsman, Marc and Humphrey, Jack and Biessels, Geert Jan and Jian, Xueqiu and Johansson, Charlotte and Jun, Gyungah R and Kastumata, Yuriko and Kauwe, John and Kehoe, Patrick G and Kilander, Lena and St{\r a}hlbom, Anne Kinhult and Kivipelto, Miia and Koivisto, Anne and Kornhuber, Johannes and Kosmidis, Mary H and Kukull, Walter A and Kuksa, Pavel P and Kunkle, Brian W and Kuzma, Amanda B and Lage, Carmen and Laukka, Erika J and Launer, Lenore and Lauria, Alessandra and Lee, Chien-Yueh and Lehtisalo, Jenni and Lerch, Ondrej and Lleo, Alberto and Longstreth, William and Lopez, Oscar and de Munain, Adolfo Lopez and Love, Seth and L{\"o}wemark, Malin and Luckcuck, Lauren and Lunetta, Kathryn L and Ma, Yiyi and Mac{\'\i}as, Juan and MacLeod, Catherine A and Maier, Wolfgang and Mangialasche, Francesca and Spallazzi, Marco and Marqui{\'e}, Marta and Marshall, Rachel and Martin, Eden R and Montes, Angel Mart{\'\i}n and Rodr{\'\i}guez, Carmen Mart{\'\i}nez and Masullo, Carlo and Mayeux, Richard and Mead, Simon and Mecocci, Patrizia and Medina, Miguel and Meggy, Alun and Mehrabian, Shima and Mendoza, Silvia and Men{\'e}ndez-Gonz{\'a}lez, Manuel and Mir, Pablo and Moebus, Susanne and Mol, Merel and Molina-Porcel, Laura and Montrreal, Laura and Morelli, Laura and Moreno, Fermin and Morgan, Kevin and Mosley, Thomas and N{\"o}then, Markus M and Muchnik, Carolina and Mukherjee, Shubhabrata and Nacmias, Benedetta and Ngandu, Tiia and Nicolas, Ga{\"e}l and Nordestgaard, B{\o}rge G and Olaso, Robert and Orellana, Adelina and Orsini, Michela and Ortega, Gemma and Padovani, Alessandro and Paolo, Caffarra and Papenberg, Goran and Parnetti, Lucilla and Pasquier, Florence and Pastor, Pau and Peloso, Gina and P{\'e}rez-Cord{\'o}n, Alba and P{\'e}rez-Tur, Jordi and Pericard, Pierre and Peters, Oliver and Pijnenburg, Yolande A L and Pineda, Juan A and Pi{\~n}ol-Ripoll, Gerard and Pisanu, Claudia and Polak, Thomas and Popp, Julius and Posthuma, Danielle and Priller, Josef and Puerta, Raquel and Quenez, Olivier and Quintela, In{\'e}s and Thomassen, Jesper Qvist and R{\'a}bano, Alberto and Rainero, Innocenzo and Rajabli, Farid and Ramakers, Inez and Real, Luis M and Reinders, Marcel J T and Reitz, Christiane and Reyes-Dumeyer, Dolly and Ridge, Perry and Riedel-Heller, Steffi and Riederer, Peter and Roberto, Natalia and Rodriguez-Rodriguez, Eloy and Rongve, Arvid and Allende, Irene Rosas and Rosende-Roca, Mait{\'e}e and Royo, Jose Luis and Rubino, Elisa and Rujescu, Dan and S{\'a}ez, Mar{\'\i}a Eugenia and Sakka, Paraskevi and Saltvedt, Ingvild and Sanabria, {\'A}ngela and S{\'a}nchez-Arjona, Mar{\'\i}a Bernal and Sanchez-Garcia, Florentino and Juan, Pascual S{\'a}nchez and S{\'a}nchez-Valle, Raquel and Sando, Sigrid B and Sarnowski, Chloe and Satizabal, Claudia L and Scamosci, Michela and Scarmeas, Nikolaos and Scarpini, Elio and Scheltens, Philip and Scherbaum, Norbert and Scherer, Martin and Schmid, Matthias and Schneider, Anja and Schott, Jonathan M and Selb{\ae}k, Geir and Seripa, Davide and Serrano, Manuel and Sha, Jin and Shadrin, Alexey A and Skrobot, Olivia and Slifer, Susan and Snijders, Gijsje J L and Soininen, Hilkka and Solfrizzi, Vincenzo and Solomon, Alina and Song, Yeunjoo and Sorbi, Sandro and Sotolongo-Grau, Oscar and Spalletta, Gianfranco and Spottke, Annika and Squassina, Alessio and Stordal, Eystein and Tartan, Juan Pablo and Tarraga, Lluis and Tes{\'\i}, Niccolo and Thalamuthu, Anbupalam and Thomas, Tegos and Tosto, Giuseppe and Traykov, Latchezar and Tremolizzo, Lucio and Tybj{\ae}rg-Hansen, Anne and Uitterlinden, Andre and Ullgren, Abbe and Ulstein, Ingun and Valero, Sergi and Valladares, Otto and Broeckhoven, Christine Van and Vance, Jeffery and Vardarajan, Badri N and van der Lugt, Aad and Dongen, Jasper Van and van Rooij, Jeroen and van Swieten, John and Vandenberghe, Rik and Verhey, Frans and Vidal, Jean-S{\'e}bastien and Vogelgsang, Jonathan and Vyhnalek, Martin and Wagner, Michael and Wallon, David and Wang, Li-San and Wang, Ruiqi and Weinhold, Leonie and Wiltfang, Jens and Windle, Gill and Woods, Bob and Yannakoulia, Mary and Zare, Habil and Zhao, Yi and Zhang, Xiaoling and Zhu, Congcong and Zulaica, Miren and Farrer, Lindsay A and Psaty, Bruce M and Ghanbari, Mohsen and Raj, Towfique and Sachdev, Perminder and Mather, Karen and Jessen, Frank and Ikram, M Arfan and de Mendon{\c c}a, Alexandre and Hort, Jakub and Tsolaki, Magda and Pericak-Vance, Margaret A and Amouyel, Philippe and Williams, Julie and Frikke-Schmidt, Ruth and Clarimon, Jordi and Deleuze, Jean-Francois and Rossi, Giacomina and Seshadri, Sudha and Andreassen, Ole A and Ingelsson, Martin and Hiltunen, Mikko and Sleegers, Kristel and Schellenberg, Gerard D and van Duijn, Cornelia M and Sims, Rebecca and van der Flier, Wiesje M and Ruiz, Agustin and Ramirez, Alfredo and Lambert, Jean-Charles} }