@article {6599, title = {Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia.}, journal = {Am J Hum Genet}, volume = {95}, year = {2014}, month = {2014 Jul 03}, pages = {24-38}, abstract = {

Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p <= 5 {\texttimes} 10(-8)) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 {\texttimes} 10(-4)) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.

}, keywords = {Adolescent, Adult, Age Factors, Aged, Blood Pressure, Cohort Studies, Humans, Middle Aged, Young Adult}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2014.05.010}, author = {Simino, Jeannette and Shi, Gang and Bis, Joshua C and Chasman, Daniel I and Ehret, Georg B and Gu, Xiangjun and Guo, Xiuqing and Hwang, Shih-Jen and Sijbrands, Eric and Smith, Albert V and Verwoert, Germaine C and Bragg-Gresham, Jennifer L and Cadby, Gemma and Chen, Peng and Cheng, Ching-Yu and Corre, Tanguy and de Boer, Rudolf A and Goel, Anuj and Johnson, Toby and Khor, Chiea-Chuen and Llu{\'\i}s-Ganella, Carla and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Nolte, Ilja M and Sim, Xueling and S{\~o}ber, Siim and van der Most, Peter J and Verweij, Niek and Zhao, Jing Hua and Amin, Najaf and Boerwinkle, Eric and Bouchard, Claude and Dehghan, Abbas and Eiriksdottir, Gudny and Elosua, Roberto and Franco, Oscar H and Gieger, Christian and Harris, Tamara B and Hercberg, Serge and Hofman, Albert and James, Alan L and Johnson, Andrew D and K{\"a}h{\"o}nen, Mika and Khaw, Kay-Tee and Kutalik, Zolt{\'a}n and Larson, Martin G and Launer, Lenore J and Li, Guo and Liu, Jianjun and Liu, Kiang and Morrison, Alanna C and Navis, Gerjan and Ong, Rick Twee-Hee and Papanicolau, George J and Penninx, Brenda W and Psaty, Bruce M and Raffel, Leslie J and Raitakari, Olli T and Rice, Kenneth and Rivadeneira, Fernando and Rose, Lynda M and Sanna, Serena and Scott, Robert A and Siscovick, David S and Stolk, Ronald P and Uitterlinden, Andr{\'e} G and Vaidya, Dhananjay and van der Klauw, Melanie M and Vasan, Ramachandran S and Vithana, Eranga Nishanthie and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Watkins, Hugh and Young, Terri L and Aung, Tin and Bochud, Murielle and Farrall, Martin and Hartman, Catharina A and Laan, Maris and Lakatta, Edward G and Lehtim{\"a}ki, Terho and Loos, Ruth J F and Lucas, Gavin and Meneton, Pierre and Palmer, Lyle J and Rettig, Rainer and Snieder, Harold and Tai, E Shyong and Teo, Yik-Ying and van der Harst, Pim and Wareham, Nicholas J and Wijmenga, Cisca and Wong, Tien Yin and Fornage, Myriam and Gudnason, Vilmundur and Levy, Daniel and Palmas, Walter and Ridker, Paul M and Rotter, Jerome I and van Duijn, Cornelia M and Witteman, Jacqueline C M and Chakravarti, Aravinda and Rao, Dabeeru C} } @article {7579, title = {Genetic loci associated with heart rate variability and their effects on cardiac disease risk.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 Jun 14}, pages = {15805}, abstract = {

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6\% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74}, issn = {2041-1723}, doi = {10.1038/ncomms15805}, author = {Nolte, Ilja M and Munoz, M Loretto and Tragante, Vinicius and Amare, Azmeraw T and Jansen, Rick and Vaez, Ahmad and von der Heyde, Benedikt and Avery, Christy L and Bis, Joshua C and Dierckx, Bram and van Dongen, Jenny and Gogarten, Stephanie M and Goyette, Philippe and Hernesniemi, Jussi and Huikari, Ville and Hwang, Shih-Jen and Jaju, Deepali and Kerr, Kathleen F and Kluttig, Alexander and Krijthe, Bouwe P and Kumar, Jitender and van der Laan, Sander W and Lyytik{\"a}inen, Leo-Pekka and Maihofer, Adam X and Minassian, Arpi and van der Most, Peter J and M{\"u}ller-Nurasyid, Martina and Nivard, Michel and Salvi, Erika and Stewart, James D and Thayer, Julian F and Verweij, Niek and Wong, Andrew and Zabaneh, Delilah and Zafarmand, Mohammad H and Abdellaoui, Abdel and Albarwani, Sulayma and Albert, Christine and Alonso, Alvaro and Ashar, Foram and Auvinen, Juha and Axelsson, Tomas and Baker, Dewleen G and de Bakker, Paul I W and Barcella, Matteo and Bayoumi, Riad and Bieringa, Rob J and Boomsma, Dorret and Boucher, Gabrielle and Britton, Annie R and Christophersen, Ingrid and Dietrich, Andrea and Ehret, George B and Ellinor, Patrick T and Eskola, Markku and Felix, Janine F and Floras, John S and Franco, Oscar H and Friberg, Peter and Gademan, Maaike G J and Geyer, Mark A and Giedraitis, Vilmantas and Hartman, Catharina A and Hemerich, Daiane and Hofman, Albert and Hottenga, Jouke-Jan and Huikuri, Heikki and Hutri-K{\"a}h{\"o}nen, Nina and Jouven, Xavier and Junttila, Juhani and Juonala, Markus and Kiviniemi, Antti M and Kors, Jan A and Kumari, Meena and Kuznetsova, Tatiana and Laurie, Cathy C and Lefrandt, Joop D and Li, Yong and Li, Yun and Liao, Duanping and Limacher, Marian C and Lin, Henry J and Lindgren, Cecilia M and Lubitz, Steven A and Mahajan, Anubha and McKnight, Barbara and Zu Schwabedissen, Henriette Meyer and Milaneschi, Yuri and Mononen, Nina and Morris, Andrew P and Nalls, Mike A and Navis, Gerjan and Neijts, Melanie and Nikus, Kjell and North, Kari E and O{\textquoteright}Connor, Daniel T and Ormel, Johan and Perz, Siegfried and Peters, Annette and Psaty, Bruce M and Raitakari, Olli T and Risbrough, Victoria B and Sinner, Moritz F and Siscovick, David and Smit, Johannes H and Smith, Nicholas L and Soliman, Elsayed Z and Sotoodehnia, Nona and Staessen, Jan A and Stein, Phyllis K and Stilp, Adrienne M and Stolarz-Skrzypek, Katarzyna and Strauch, Konstantin and Sundstr{\"o}m, Johan and Swenne, Cees A and Syv{\"a}nen, Ann-Christine and Tardif, Jean-Claude and Taylor, Kent D and Teumer, Alexander and Thornton, Timothy A and Tinker, Lesley E and Uitterlinden, Andr{\'e} G and van Setten, Jessica and Voss, Andreas and Waldenberger, Melanie and Wilhelmsen, Kirk C and Willemsen, Gonneke and Wong, Quenna and Zhang, Zhu-Ming and Zonderman, Alan B and Cusi, Daniele and Evans, Michele K and Greiser, Halina K and van der Harst, Pim and Hassan, Mohammad and Ingelsson, Erik and Jarvelin, Marjo-Riitta and K{\"a}{\"a}b, Stefan and K{\"a}h{\"o}nen, Mika and Kivimaki, Mika and Kooperberg, Charles and Kuh, Diana and Lehtim{\"a}ki, Terho and Lind, Lars and Nievergelt, Caroline M and O{\textquoteright}Donnell, Chris J and Oldehinkel, Albertine J and Penninx, Brenda and Reiner, Alexander P and Riese, Harri{\"e}tte and van Roon, Arie M and Rioux, John D and Rotter, Jerome I and Sofer, Tamar and Stricker, Bruno H and Tiemeier, Henning and Vrijkotte, Tanja G M and Asselbergs, Folkert W and Brundel, Bianca J J M and Heckbert, Susan R and Whitsel, Eric A and den Hoed, Marcel and Snieder, Harold and de Geus, Eco J C} } @article {7845, title = {Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.}, journal = {Nat Genet}, volume = {50}, year = {2018}, month = {2018 Oct}, pages = {1412-1425}, abstract = {

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

}, issn = {1546-1718}, doi = {10.1038/s41588-018-0205-x}, author = {Evangelou, Evangelos and Warren, Helen R and Mosen-Ansorena, David and Mifsud, Borbala and Pazoki, Raha and Gao, He and Ntritsos, Georgios and Dimou, Niki and Cabrera, Claudia P and Karaman, Ibrahim and Ng, Fu Liang and Evangelou, Marina and Witkowska, Katarzyna and Tzanis, Evan and Hellwege, Jacklyn N and Giri, Ayush and Velez Edwards, Digna R and Sun, Yan V and Cho, Kelly and Gaziano, J Michael and Wilson, Peter W F and Tsao, Philip S and Kovesdy, Csaba P and Esko, T{\~o}nu and M{\"a}gi, Reedik and Milani, Lili and Almgren, Peter and Boutin, Thibaud and Debette, Stephanie and Ding, Jun and Giulianini, Franco and Holliday, Elizabeth G and Jackson, Anne U and Li-Gao, Ruifang and Lin, Wei-Yu and Luan, Jian{\textquoteright}an and Mangino, Massimo and Oldmeadow, Christopher and Prins, Bram Peter and Qian, Yong and Sargurupremraj, Muralidharan and Shah, Nabi and Surendran, Praveen and Th{\'e}riault, S{\'e}bastien and Verweij, Niek and Willems, Sara M and Zhao, Jing-Hua and Amouyel, Philippe and Connell, John and de Mutsert, Ren{\'e}e and Doney, Alex S F and Farrall, Martin and Menni, Cristina and Morris, Andrew D and Noordam, Raymond and Par{\'e}, Guillaume and Poulter, Neil R and Shields, Denis C and Stanton, Alice and Thom, Simon and Abecasis, Goncalo and Amin, Najaf and Arking, Dan E and Ayers, Kristin L and Barbieri, Caterina M and Batini, Chiara and Bis, Joshua C and Blake, Tineka and Bochud, Murielle and Boehnke, Michael and Boerwinkle, Eric and Boomsma, Dorret I and Bottinger, Erwin P and Braund, Peter S and Brumat, Marco and Campbell, Archie and Campbell, Harry and Chakravarti, Aravinda and Chambers, John C and Chauhan, Ganesh and Ciullo, Marina and Cocca, Massimiliano and Collins, Francis and Cordell, Heather J and Davies, Gail and Borst, Martin H de and Geus, Eco J de and Deary, Ian J and Deelen, Joris and del Greco M, Fabiola and Demirkale, Cumhur Yusuf and D{\"o}rr, Marcus and Ehret, Georg B and Elosua, Roberto and Enroth, Stefan and Erzurumluoglu, A Mesut and Ferreira, Teresa and Fr{\r a}nberg, Mattias and Franco, Oscar H and Gandin, Ilaria and Gasparini, Paolo and Giedraitis, Vilmantas and Gieger, Christian and Girotto, Giorgia and Goel, Anuj and Gow, Alan J and Gudnason, Vilmundur and Guo, Xiuqing and Gyllensten, Ulf and Hamsten, Anders and Harris, Tamara B and Harris, Sarah E and Hartman, Catharina A and Havulinna, Aki S and Hicks, Andrew A and Hofer, Edith and Hofman, Albert and Hottenga, Jouke-Jan and Huffman, Jennifer E and Hwang, Shih-Jen and Ingelsson, Erik and James, Alan and Jansen, Rick and Jarvelin, Marjo-Riitta and Joehanes, Roby and Johansson, Asa and Johnson, Andrew D and Joshi, Peter K and Jousilahti, Pekka and Jukema, J Wouter and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kathiresan, Sekar and Keavney, Bernard D and Khaw, Kay-Tee and Knekt, Paul and Knight, Joanne and Kolcic, Ivana and Kooner, Jaspal S and Koskinen, Seppo and Kristiansson, Kati and Kutalik, Zolt{\'a}n and Laan, Maris and Larson, Marty and Launer, Lenore J and Lehne, Benjamin and Lehtim{\"a}ki, Terho and Liewald, David C M and Lin, Li and Lind, Lars and Lindgren, Cecilia M and Liu, Yongmei and Loos, Ruth J F and Lopez, Lorna M and Lu, Yingchang and Lyytik{\"a}inen, Leo-Pekka and Mahajan, Anubha and Mamasoula, Chrysovalanto and Marrugat, Jaume and Marten, Jonathan and Milaneschi, Yuri and Morgan, Anna and Morris, Andrew P and Morrison, Alanna C and Munson, Peter J and Nalls, Mike A and Nandakumar, Priyanka and Nelson, Christopher P and Niiranen, Teemu and Nolte, Ilja M and Nutile, Teresa and Oldehinkel, Albertine J and Oostra, Ben A and O{\textquoteright}Reilly, Paul F and Org, Elin and Padmanabhan, Sandosh and Palmas, Walter and Palotie, Aarno and Pattie, Alison and Penninx, Brenda W J H and Perola, Markus and Peters, Annette and Polasek, Ozren and Pramstaller, Peter P and Nguyen, Quang Tri and Raitakari, Olli T and Ren, Meixia and Rettig, Rainer and Rice, Kenneth and Ridker, Paul M and Ried, Janina S and Riese, Harri{\"e}tte and Ripatti, Samuli and Robino, Antonietta and Rose, Lynda M and Rotter, Jerome I and Rudan, Igor and Ruggiero, Daniela and Saba, Yasaman and Sala, Cinzia F and Salomaa, Veikko and Samani, Nilesh J and Sarin, Antti-Pekka and Schmidt, Reinhold and Schmidt, Helena and Shrine, Nick and Siscovick, David and Smith, Albert V and Snieder, Harold and S{\~o}ber, Siim and Sorice, Rossella and Starr, John M and Stott, David J and Strachan, David P and Strawbridge, Rona J and Sundstr{\"o}m, Johan and Swertz, Morris A and Taylor, Kent D and Teumer, Alexander and Tobin, Martin D and Tomaszewski, Maciej and Toniolo, Daniela and Traglia, Michela and Trompet, Stella and Tuomilehto, Jaakko and Tzourio, Christophe and Uitterlinden, Andr{\'e} G and Vaez, Ahmad and van der Most, Peter J and van Duijn, Cornelia M and Vergnaud, Anne-Claire and Verwoert, Germaine C and Vitart, Veronique and V{\"o}lker, Uwe and Vollenweider, Peter and Vuckovic, Dragana and Watkins, Hugh and Wild, Sarah H and Willemsen, Gonneke and Wilson, James F and Wright, Alan F and Yao, Jie and Zemunik, Tatijana and Zhang, Weihua and Attia, John R and Butterworth, Adam S and Chasman, Daniel I and Conen, David and Cucca, Francesco and Danesh, John and Hayward, Caroline and Howson, Joanna M M and Laakso, Markku and Lakatta, Edward G and Langenberg, Claudia and Melander, Olle and Mook-Kanamori, Dennis O and Palmer, Colin N A and Risch, Lorenz and Scott, Robert A and Scott, Rodney J and Sever, Peter and Spector, Tim D and van der Harst, Pim and Wareham, Nicholas J and Zeggini, Eleftheria and Levy, Daniel and Munroe, Patricia B and Newton-Cheh, Christopher and Brown, Morris J and Metspalu, Andres and Hung, Adriana M and O{\textquoteright}Donnell, Christopher J and Edwards, Todd L and Psaty, Bruce M and Tzoulaki, Ioanna and Barnes, Michael R and Wain, Louise V and Elliott, Paul and Caulfield, Mark J} } @article {7920, title = {Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.}, journal = {Am J Hum Genet}, volume = {103}, year = {2018}, month = {2018 Nov 01}, pages = {691-706}, abstract = {

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5~{\texttimes} 10). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0\% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2018.09.009}, author = {Ligthart, Symen and Vaez, Ahmad and V{\~o}sa, Urmo and Stathopoulou, Maria G and de Vries, Paul S and Prins, Bram P and van der Most, Peter J and Tanaka, Toshiko and Naderi, Elnaz and Rose, Lynda M and Wu, Ying and Karlsson, Robert and Barbalic, Maja and Lin, Honghuang and Pool, Rene and Zhu, Gu and Mace, Aurelien and Sidore, Carlo and Trompet, Stella and Mangino, Massimo and Sabater-Lleal, Maria and Kemp, John P and Abbasi, Ali and Kacprowski, Tim and Verweij, Niek and Smith, Albert V and Huang, Tao and Marzi, Carola and Feitosa, Mary F and Lohman, Kurt K and Kleber, Marcus E and Milaneschi, Yuri and Mueller, Christian and Huq, Mahmudul and Vlachopoulou, Efthymia and Lyytik{\"a}inen, Leo-Pekka and Oldmeadow, Christopher and Deelen, Joris and Perola, Markus and Zhao, Jing Hua and Feenstra, Bjarke and Amini, Marzyeh and Lahti, Jari and Schraut, Katharina E and Fornage, Myriam and Suktitipat, Bhoom and Chen, Wei-Min and Li, Xiaohui and Nutile, Teresa and Malerba, Giovanni and Luan, Jian{\textquoteright}an and Bak, Tom and Schork, Nicholas and del Greco M, Fabiola and Thiering, Elisabeth and Mahajan, Anubha and Marioni, Riccardo E and Mihailov, Evelin and Eriksson, Joel and Ozel, Ayse Bilge and Zhang, Weihua and Nethander, Maria and Cheng, Yu-Ching and Aslibekyan, Stella and Ang, Wei and Gandin, Ilaria and Yengo, Loic and Portas, Laura and Kooperberg, Charles and Hofer, Edith and Rajan, Kumar B and Schurmann, Claudia and den Hollander, Wouter and Ahluwalia, Tarunveer S and Zhao, Jing and Draisma, Harmen H M and Ford, Ian and Timpson, Nicholas and Teumer, Alexander and Huang, Hongyan and Wahl, Simone and Liu, Yongmei and Huang, Jie and Uh, Hae-Won and Geller, Frank and Joshi, Peter K and Yanek, Lisa R and Trabetti, Elisabetta and Lehne, Benjamin and Vozzi, Diego and Verbanck, Marie and Biino, Ginevra and Saba, Yasaman and Meulenbelt, Ingrid and O{\textquoteright}Connell, Jeff R and Laakso, Markku and Giulianini, Franco and Magnusson, Patrik K E and Ballantyne, Christie M and Hottenga, Jouke Jan and Montgomery, Grant W and Rivadineira, Fernando and Rueedi, Rico and Steri, Maristella and Herzig, Karl-Heinz and Stott, David J and Menni, Cristina and Fr{\r a}nberg, Mattias and St Pourcain, Beate and Felix, Stephan B and Pers, Tune H and Bakker, Stephan J L and Kraft, Peter and Peters, Annette and Vaidya, Dhananjay and Delgado, Graciela and Smit, Johannes H and Gro{\ss}mann, Vera and Sinisalo, Juha and Sepp{\"a}l{\"a}, Ilkka and Williams, Stephen R and Holliday, Elizabeth G and Moed, Matthijs and Langenberg, Claudia and R{\"a}ikk{\"o}nen, Katri and Ding, Jingzhong and Campbell, Harry and Sale, Mich{\`e}le M and Chen, Yii-der I and James, Alan L and Ruggiero, Daniela and Soranzo, Nicole and Hartman, Catharina A and Smith, Erin N and Berenson, Gerald S and Fuchsberger, Christian and Hernandez, Dena and Tiesler, Carla M T and Giedraitis, Vilmantas and Liewald, David and Fischer, Krista and Mellstr{\"o}m, Dan and Larsson, Anders and Wang, Yunmei and Scott, William R and Lorentzon, Matthias and Beilby, John and Ryan, Kathleen A and Pennell, Craig E and Vuckovic, Dragana and Balkau, Beverly and Concas, Maria Pina and Schmidt, Reinhold and Mendes de Leon, Carlos F and Bottinger, Erwin P and Kloppenburg, Margreet and Paternoster, Lavinia and Boehnke, Michael and Musk, A W and Willemsen, Gonneke and Evans, David M and Madden, Pamela A F and K{\"a}h{\"o}nen, Mika and Kutalik, Zolt{\'a}n and Zoledziewska, Magdalena and Karhunen, Ville and Kritchevsky, Stephen B and Sattar, Naveed and Lachance, Genevieve and Clarke, Robert and Harris, Tamara B and Raitakari, Olli T and Attia, John R and van Heemst, Diana and Kajantie, Eero and Sorice, Rossella and Gambaro, Giovanni and Scott, Robert A and Hicks, Andrew A and Ferrucci, Luigi and Standl, Marie and Lindgren, Cecilia M and Starr, John M and Karlsson, Magnus and Lind, Lars and Li, Jun Z and Chambers, John C and Mori, Trevor A and de Geus, Eco J C N and Heath, Andrew C and Martin, Nicholas G and Auvinen, Juha and Buckley, Brendan M and de Craen, Anton J M and Waldenberger, Melanie and Strauch, Konstantin and Meitinger, Thomas and Scott, Rodney J and McEvoy, Mark and Beekman, Marian and Bombieri, Cristina and Ridker, Paul M and Mohlke, Karen L and Pedersen, Nancy L and Morrison, Alanna C and Boomsma, Dorret I and Whitfield, John B and Strachan, David P and Hofman, Albert and Vollenweider, Peter and Cucca, Francesco and Jarvelin, Marjo-Riitta and Jukema, J Wouter and Spector, Tim D and Hamsten, Anders and Zeller, Tanja and Uitterlinden, Andr{\'e} G and Nauck, Matthias and Gudnason, Vilmundur and Qi, Lu and Grallert, Harald and Borecki, Ingrid B and Rotter, Jerome I and M{\"a}rz, Winfried and Wild, Philipp S and Lokki, Marja-Liisa and Boyle, Michael and Salomaa, Veikko and Melbye, Mads and Eriksson, Johan G and Wilson, James F and Penninx, Brenda W J H and Becker, Diane M and Worrall, Bradford B and Gibson, Greg and Krauss, Ronald M and Ciullo, Marina and Zaza, Gianluigi and Wareham, Nicholas J and Oldehinkel, Albertine J and Palmer, Lyle J and Murray, Sarah S and Pramstaller, Peter P and Bandinelli, Stefania and Heinrich, Joachim and Ingelsson, Erik and Deary, Ian J and M{\"a}gi, Reedik and Vandenput, Liesbeth and van der Harst, Pim and Desch, Karl C and Kooner, Jaspal S and Ohlsson, Claes and Hayward, Caroline and Lehtim{\"a}ki, Terho and Shuldiner, Alan R and Arnett, Donna K and Beilin, Lawrence J and Robino, Antonietta and Froguel, Philippe and Pirastu, Mario and Jess, Tine and Koenig, Wolfgang and Loos, Ruth J F and Evans, Denis A and Schmidt, Helena and Smith, George Davey and Slagboom, P Eline and Eiriksdottir, Gudny and Morris, Andrew P and Psaty, Bruce M and Tracy, Russell P and Nolte, Ilja M and Boerwinkle, Eric and Visvikis-Siest, Sophie and Reiner, Alex P and Gross, Myron and Bis, Joshua C and Franke, Lude and Franco, Oscar H and Benjamin, Emelia J and Chasman, Daniel I and Dupuis, Jos{\'e}e and Snieder, Harold and Dehghan, Abbas and Alizadeh, Behrooz Z} } @article {9093, title = {Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies.}, journal = {Kidney Int}, year = {2022}, month = {2022 Jun 16}, abstract = {

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95\% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95\% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.

}, issn = {1523-1755}, doi = {10.1016/j.kint.2022.05.021}, author = {Gorski, Mathias and Rasheed, Humaira and Teumer, Alexander and Thomas, Laurent F and Graham, Sarah E and Sveinbjornsson, Gardar and Winkler, Thomas W and G{\"u}nther, Felix and Stark, Klaus J and Chai, Jin-Fang and Tayo, Bamidele O and Wuttke, Matthias and Li, Yong and Tin, Adrienne and Ahluwalia, Tarunveer S and Arnl{\"o}v, Johan and {\r A}svold, Bj{\o}rn Olav and Bakker, Stephan J L and Banas, Bernhard and Bansal, Nisha and Biggs, Mary L and Biino, Ginevra and B{\"o}hnke, Michael and Boerwinkle, Eric and Bottinger, Erwin P and Brenner, Hermann and Brumpton, Ben and Carroll, Robert J and Chaker, Layal and Chalmers, John and Chee, Miao-Li and Chee, Miao-Ling and Cheng, Ching-Yu and Chu, Audrey Y and Ciullo, Marina and Cocca, Massimiliano and Cook, James P and Coresh, Josef and Cusi, Daniele and de Borst, Martin H and Degenhardt, Frauke and Eckardt, Kai-Uwe and Endlich, Karlhans and Evans, Michele K and Feitosa, Mary F and Franke, Andre and Freitag-Wolf, Sandra and Fuchsberger, Christian and Gampawar, Piyush and Gansevoort, Ron T and Ghanbari, Mohsen and Ghasemi, Sahar and Giedraitis, Vilmantas and Gieger, Christian and Gudbjartsson, Daniel F and Hallan, Stein and Hamet, Pavel and Hishida, Asahi and Ho, Kevin and Hofer, Edith and Holleczek, Bernd and Holm, Hilma and Hoppmann, Anselm and Horn, Katrin and Hutri-K{\"a}h{\"o}nen, Nina and Hveem, Kristian and Hwang, Shih-Jen and Ikram, M Arfan and Josyula, Navya Shilpa and Jung, Bettina and K{\"a}h{\"o}nen, Mika and Karabegovi{\'c}, Irma and Khor, Chiea-Chuen and Koenig, Wolfgang and Kramer, Holly and Kr{\"a}mer, Bernhard K and Kuhnel, Brigitte and Kuusisto, Johanna and Laakso, Markku and Lange, Leslie A and Lehtim{\"a}ki, Terho and Li, Man and Lieb, Wolfgang and Lind, Lars and Lindgren, Cecilia M and Loos, Ruth J F and Lukas, Mary Ann and Lyytik{\"a}inen, Leo-Pekka and Mahajan, Anubha and Matias-Garcia, Pamela R and Meisinger, Christa and Meitinger, Thomas and Melander, Olle and Milaneschi, Yuri and Mishra, Pashupati P and Mononen, Nina and Morris, Andrew P and Mychaleckyj, Josyf C and Nadkarni, Girish N and Naito, Mariko and Nakatochi, Masahiro and Nalls, Mike A and Nauck, Matthias and Nikus, Kjell and Ning, Boting and Nolte, Ilja M and Nutile, Teresa and O{\textquoteright}Donoghue, Michelle L and O{\textquoteright}Connell, Jeffrey and Olafsson, Isleifur and Orho-Melander, Marju and Parsa, Afshin and Pendergrass, Sarah A and Penninx, Brenda W J H and Pirastu, Mario and Preuss, Michael H and Psaty, Bruce M and Raffield, Laura M and Raitakari, Olli T and Rheinberger, Myriam and Rice, Kenneth M and Rizzi, Federica and Rosenkranz, Alexander R and Rossing, Peter and Rotter, Jerome I and Ruggiero, Daniela and Ryan, Kathleen A and Sabanayagam, Charumathi and Salvi, Erika and Schmidt, Helena and Schmidt, Reinhold and Scholz, Markus and Sch{\"o}ttker, Ben and Schulz, Christina-Alexandra and Sedaghat, Sanaz and Shaffer, Christian M and Sieber, Karsten B and Sim, Xueling and Sims, Mario and Snieder, Harold and Stanzick, Kira J and Thorsteinsdottir, Unnur and Stocker, Hannah and Strauch, Konstantin and Stringham, Heather M and Sulem, Patrick and Szymczak, Silke and Taylor, Kent D and Thio, Chris H L and Tremblay, Johanne and Vaccargiu, Simona and van der Harst, Pim and van der Most, Peter J and Verweij, Niek and V{\"o}lker, Uwe and Wakai, Kenji and Waldenberger, Melanie and Wallentin, Lars and Wallner, Stefan and Wang, Judy and Waterworth, Dawn M and White, Harvey D and Willer, Cristen J and Wong, Tien-Yin and Woodward, Mark and Yang, Qiong and Yerges-Armstrong, Laura M and Zimmermann, Martina and Zonderman, Alan B and Bergler, Tobias and Stefansson, Kari and B{\"o}ger, Carsten A and Pattaro, Cristian and K{\"o}ttgen, Anna and Kronenberg, Florian and Heid, Iris M} } @article {9535, title = {Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.}, journal = {Front Genet}, volume = {14}, year = {2023}, month = {2023}, pages = {1235337}, abstract = {

Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant ( < 5 {\texttimes} 10) and suggestive ( < 1 {\texttimes} 10) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (), brain (), and liver () biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

}, issn = {1664-8021}, doi = {10.3389/fgene.2023.1235337}, author = {de Las Fuentes, Lisa and Schwander, Karen L and Brown, Michael R and Bentley, Amy R and Winkler, Thomas W and Sung, Yun Ju and Munroe, Patricia B and Miller, Clint L and Aschard, Hugo and Aslibekyan, Stella and Bartz, Traci M and Bielak, Lawrence F and Chai, Jin Fang and Cheng, Ching-Yu and Dorajoo, Rajkumar and Feitosa, Mary F and Guo, Xiuqing and Hartwig, Fernando P and Horimoto, Andrea and Kolcic, Ivana and Lim, Elise and Liu, Yongmei and Manning, Alisa K and Marten, Jonathan and Musani, Solomon K and Noordam, Raymond and Padmanabhan, Sandosh and Rankinen, Tuomo and Richard, Melissa A and Ridker, Paul M and Smith, Albert V and Vojinovic, Dina and Zonderman, Alan B and Alver, Maris and Boissel, Mathilde and Christensen, Kaare and Freedman, Barry I and Gao, Chuan and Giulianini, Franco and Harris, Sarah E and He, Meian and Hsu, Fang-Chi and Kuhnel, Brigitte and Laguzzi, Federica and Li, Xiaoyin and Lyytik{\"a}inen, Leo-Pekka and Nolte, Ilja M and Poveda, Alaitz and Rauramaa, Rainer and Riaz, Muhammad and Robino, Antonietta and Sofer, Tamar and Takeuchi, Fumihiko and Tayo, Bamidele O and van der Most, Peter J and Verweij, Niek and Ware, Erin B and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Zhan, Yiqiang and Amin, Najaf and Arking, Dan E and Ballantyne, Christie and Boerwinkle, Eric and Brody, Jennifer A and Broeckel, Ulrich and Campbell, Archie and Canouil, Micka{\"e}l and Chai, Xiaoran and Chen, Yii-Der Ida and Chen, Xu and Chitrala, Kumaraswamy Naidu and Concas, Maria Pina and de Faire, Ulf and de Mutsert, Ren{\'e}e and de Silva, H Janaka and de Vries, Paul S and Do, Ahn and Faul, Jessica D and Fisher, Virginia and Floyd, James S and Forrester, Terrence and Friedlander, Yechiel and Girotto, Giorgia and Gu, C Charles and Hallmans, G{\"o}ran and Heikkinen, Sami and Heng, Chew-Kiat and Homuth, Georg and Hunt, Steven and Ikram, M Arfan and Jacobs, David R and Kavousi, Maryam and Khor, Chiea Chuen and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Komulainen, Pirjo and Langefeld, Carl D and Liang, Jingjing and Liu, Kiang and Liu, Jianjun and Lohman, Kurt and M{\"a}gi, Reedik and Manichaikul, Ani W and McKenzie, Colin A and Meitinger, Thomas and Milaneschi, Yuri and Nauck, Matthias and Nelson, Christopher P and O{\textquoteright}Connell, Jeffrey R and Palmer, Nicholette D and Pereira, Alexandre C and Perls, Thomas and Peters, Annette and Polasek, Ozren and Raitakari, Olli T and Rice, Kenneth and Rice, Treva K and Rich, Stephen S and Sabanayagam, Charumathi and Schreiner, Pamela J and Shu, Xiao-Ou and Sidney, Stephen and Sims, Mario and Smith, Jennifer A and Starr, John M and Strauch, Konstantin and Tai, E Shyong and Taylor, Kent D and Tsai, Michael Y and Uitterlinden, Andr{\'e} G and van Heemst, Diana and Waldenberger, Melanie and Wang, Ya-Xing and Wei, Wen-Bin and Wilson, Gregory and Xuan, Deng and Yao, Jie and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Becker, Diane M and Bonnefond, Am{\'e}lie and Bowden, Donald W and Cooper, Richard S and Deary, Ian J and Divers, Jasmin and Esko, T{\~o}nu and Franks, Paul W and Froguel, Philippe and Gieger, Christian and Jonas, Jost B and Kato, Norihiro and Lakka, Timo A and Leander, Karin and Lehtim{\"a}ki, Terho and Magnusson, Patrik K E and North, Kari E and Ntalla, Ioanna and Penninx, Brenda and Samani, Nilesh J and Snieder, Harold and Spedicati, Beatrice and van der Harst, Pim and V{\"o}lzke, Henry and Wagenknecht, Lynne E and Weir, David R and Wojczynski, Mary K and Wu, Tangchun and Zheng, Wei and Zhu, Xiaofeng and Bouchard, Claude and Chasman, Daniel I and Evans, Michele K and Fox, Ervin R and Gudnason, Vilmundur and Hayward, Caroline and Horta, Bernardo L and Kardia, Sharon L R and Krieger, Jose Eduardo and Mook-Kanamori, Dennis O and Peyser, Patricia A and Province, Michael M and Psaty, Bruce M and Rudan, Igor and Sim, Xueling and Smith, Blair H and van Dam, Rob M and van Duijn, Cornelia M and Wong, Tien Yin and Arnett, Donna K and Rao, Dabeeru C and Gauderman, James and Liu, Ching-Ti and Morrison, Alanna C and Rotter, Jerome I and Fornage, Myriam} }