%0 Journal Article %J Nature %D 2010 %T Biological, clinical and population relevance of 95 loci for blood lipids. %A Teslovich, Tanya M %A Musunuru, Kiran %A Smith, Albert V %A Edmondson, Andrew C %A Stylianou, Ioannis M %A Koseki, Masahiro %A Pirruccello, James P %A Ripatti, Samuli %A Chasman, Daniel I %A Willer, Cristen J %A Johansen, Christopher T %A Fouchier, Sigrid W %A Isaacs, Aaron %A Peloso, Gina M %A Barbalic, Maja %A Ricketts, Sally L %A Bis, Joshua C %A Aulchenko, Yurii S %A Thorleifsson, Gudmar %A Feitosa, Mary F %A Chambers, John %A Orho-Melander, Marju %A Melander, Olle %A Johnson, Toby %A Li, Xiaohui %A Guo, Xiuqing %A Li, Mingyao %A Shin Cho, Yoon %A Jin Go, Min %A Jin Kim, Young %A Lee, Jong-Young %A Park, Taesung %A Kim, Kyunga %A Sim, Xueling %A Twee-Hee Ong, Rick %A Croteau-Chonka, Damien C %A Lange, Leslie A %A Smith, Joshua D %A Song, Kijoung %A Hua Zhao, Jing %A Yuan, Xin %A Luan, Jian'an %A Lamina, Claudia %A Ziegler, Andreas %A Zhang, Weihua %A Zee, Robert Y L %A Wright, Alan F %A Witteman, Jacqueline C M %A Wilson, James F %A Willemsen, Gonneke %A Wichmann, H-Erich %A Whitfield, John B %A Waterworth, Dawn M %A Wareham, Nicholas J %A Waeber, Gérard %A Vollenweider, Peter %A Voight, Benjamin F %A Vitart, Veronique %A Uitterlinden, André G %A Uda, Manuela %A Tuomilehto, Jaakko %A Thompson, John R %A Tanaka, Toshiko %A Surakka, Ida %A Stringham, Heather M %A Spector, Tim D %A Soranzo, Nicole %A Smit, Johannes H %A Sinisalo, Juha %A Silander, Kaisa %A Sijbrands, Eric J G %A Scuteri, Angelo %A Scott, James %A Schlessinger, David %A Sanna, Serena %A Salomaa, Veikko %A Saharinen, Juha %A Sabatti, Chiara %A Ruokonen, Aimo %A Rudan, Igor %A Rose, Lynda M %A Roberts, Robert %A Rieder, Mark %A Psaty, Bruce M %A Pramstaller, Peter P %A Pichler, Irene %A Perola, Markus %A Penninx, Brenda W J H %A Pedersen, Nancy L %A Pattaro, Cristian %A Parker, Alex N %A Paré, Guillaume %A Oostra, Ben A %A O'Donnell, Christopher J %A Nieminen, Markku S %A Nickerson, Deborah A %A Montgomery, Grant W %A Meitinger, Thomas %A McPherson, Ruth %A McCarthy, Mark I %A McArdle, Wendy %A Masson, David %A Martin, Nicholas G %A Marroni, Fabio %A Mangino, Massimo %A Magnusson, Patrik K E %A Lucas, Gavin %A Luben, Robert %A Loos, Ruth J F %A Lokki, Marja-Liisa %A Lettre, Guillaume %A Langenberg, Claudia %A Launer, Lenore J %A Lakatta, Edward G %A Laaksonen, Reijo %A Kyvik, Kirsten O %A Kronenberg, Florian %A König, Inke R %A Khaw, Kay-Tee %A Kaprio, Jaakko %A Kaplan, Lee M %A Johansson, Asa %A Jarvelin, Marjo-Riitta %A Janssens, A Cecile J W %A Ingelsson, Erik %A Igl, Wilmar %A Kees Hovingh, G %A Hottenga, Jouke-Jan %A Hofman, Albert %A Hicks, Andrew A %A Hengstenberg, Christian %A Heid, Iris M %A Hayward, Caroline %A Havulinna, Aki S %A Hastie, Nicholas D %A Harris, Tamara B %A Haritunians, Talin %A Hall, Alistair S %A Gyllensten, Ulf %A Guiducci, Candace %A Groop, Leif C %A Gonzalez, Elena %A Gieger, Christian %A Freimer, Nelson B %A Ferrucci, Luigi %A Erdmann, Jeanette %A Elliott, Paul %A Ejebe, Kenechi G %A Döring, Angela %A Dominiczak, Anna F %A Demissie, Serkalem %A Deloukas, Panagiotis %A de Geus, Eco J C %A de Faire, Ulf %A Crawford, Gabriel %A Collins, Francis S %A Chen, Yii-der I %A Caulfield, Mark J %A Campbell, Harry %A Burtt, Noel P %A Bonnycastle, Lori L %A Boomsma, Dorret I %A Boekholdt, S Matthijs %A Bergman, Richard N %A Barroso, Inês %A Bandinelli, Stefania %A Ballantyne, Christie M %A Assimes, Themistocles L %A Quertermous, Thomas %A Altshuler, David %A Seielstad, Mark %A Wong, Tien Y %A Tai, E-Shyong %A Feranil, Alan B %A Kuzawa, Christopher W %A Adair, Linda S %A Taylor, Herman A %A Borecki, Ingrid B %A Gabriel, Stacey B %A Wilson, James G %A Holm, Hilma %A Thorsteinsdottir, Unnur %A Gudnason, Vilmundur %A Krauss, Ronald M %A Mohlke, Karen L %A Ordovas, Jose M %A Munroe, Patricia B %A Kooner, Jaspal S %A Tall, Alan R %A Hegele, Robert A %A Kastelein, John J P %A Schadt, Eric E %A Rotter, Jerome I %A Boerwinkle, Eric %A Strachan, David P %A Mooser, Vincent %A Stefansson, Kari %A Reilly, Muredach P %A Samani, Nilesh J %A Schunkert, Heribert %A Cupples, L Adrienne %A Sandhu, Manjinder S %A Ridker, Paul M %A Rader, Daniel J %A van Duijn, Cornelia M %A Peltonen, Leena %A Abecasis, Goncalo R %A Boehnke, Michael %A Kathiresan, Sekar %K African Americans %K Animals %K Asian Continental Ancestry Group %K Cholesterol, HDL %K Cholesterol, LDL %K Coronary Artery Disease %K Europe %K European Continental Ancestry Group %K Female %K Genetic Loci %K Genome-Wide Association Study %K Genotype %K Humans %K Lipid Metabolism %K Lipids %K Liver %K Male %K Mice %K N-Acetylgalactosaminyltransferases %K Phenotype %K Polymorphism, Single Nucleotide %K Protein Phosphatase 1 %K Reproducibility of Results %K Triglycerides %X

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

%B Nature %V 466 %P 707-13 %8 2010 Aug 05 %G eng %N 7307 %1 http://www.ncbi.nlm.nih.gov/pubmed/20686565?dopt=Abstract %R 10.1038/nature09270 %0 Journal Article %J PLoS Genet %D 2012 %T Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. %A Dastani, Zari %A Hivert, Marie-France %A Timpson, Nicholas %A Perry, John R B %A Yuan, Xin %A Scott, Robert A %A Henneman, Peter %A Heid, Iris M %A Kizer, Jorge R %A Lyytikäinen, Leo-Pekka %A Fuchsberger, Christian %A Tanaka, Toshiko %A Morris, Andrew P %A Small, Kerrin %A Isaacs, Aaron %A Beekman, Marian %A Coassin, Stefan %A Lohman, Kurt %A Qi, Lu %A Kanoni, Stavroula %A Pankow, James S %A Uh, Hae-Won %A Wu, Ying %A Bidulescu, Aurelian %A Rasmussen-Torvik, Laura J %A Greenwood, Celia M T %A Ladouceur, Martin %A Grimsby, Jonna %A Manning, Alisa K %A Liu, Ching-Ti %A Kooner, Jaspal %A Mooser, Vincent E %A Vollenweider, Peter %A Kapur, Karen A %A Chambers, John %A Wareham, Nicholas J %A Langenberg, Claudia %A Frants, Rune %A Willems-Vandijk, Ko %A Oostra, Ben A %A Willems, Sara M %A Lamina, Claudia %A Winkler, Thomas W %A Psaty, Bruce M %A Tracy, Russell P %A Brody, Jennifer %A Chen, Ida %A Viikari, Jorma %A Kähönen, Mika %A Pramstaller, Peter P %A Evans, David M %A St Pourcain, Beate %A Sattar, Naveed %A Wood, Andrew R %A Bandinelli, Stefania %A Carlson, Olga D %A Egan, Josephine M %A Böhringer, Stefan %A van Heemst, Diana %A Kedenko, Lyudmyla %A Kristiansson, Kati %A Nuotio, Marja-Liisa %A Loo, Britt-Marie %A Harris, Tamara %A Garcia, Melissa %A Kanaya, Alka %A Haun, Margot %A Klopp, Norman %A Wichmann, H-Erich %A Deloukas, Panos %A Katsareli, Efi %A Couper, David J %A Duncan, Bruce B %A Kloppenburg, Margreet %A Adair, Linda S %A Borja, Judith B %A Wilson, James G %A Musani, Solomon %A Guo, Xiuqing %A Johnson, Toby %A Semple, Robert %A Teslovich, Tanya M %A Allison, Matthew A %A Redline, Susan %A Buxbaum, Sarah G %A Mohlke, Karen L %A Meulenbelt, Ingrid %A Ballantyne, Christie M %A Dedoussis, George V %A Hu, Frank B %A Liu, Yongmei %A Paulweber, Bernhard %A Spector, Timothy D %A Slagboom, P Eline %A Ferrucci, Luigi %A Jula, Antti %A Perola, Markus %A Raitakari, Olli %A Florez, Jose C %A Salomaa, Veikko %A Eriksson, Johan G %A Frayling, Timothy M %A Hicks, Andrew A %A Lehtimäki, Terho %A Smith, George Davey %A Siscovick, David S %A Kronenberg, Florian %A van Duijn, Cornelia %A Loos, Ruth J F %A Waterworth, Dawn M %A Meigs, James B %A Dupuis, Josée %A Richards, J Brent %A Voight, Benjamin F %A Scott, Laura J %A Steinthorsdottir, Valgerdur %A Dina, Christian %A Welch, Ryan P %A Zeggini, Eleftheria %A Huth, Cornelia %A Aulchenko, Yurii S %A Thorleifsson, Gudmar %A McCulloch, Laura J %A Ferreira, Teresa %A Grallert, Harald %A Amin, Najaf %A Wu, Guanming %A Willer, Cristen J %A Raychaudhuri, Soumya %A McCarroll, Steve A %A Hofmann, Oliver M %A Segrè, Ayellet V %A van Hoek, Mandy %A Navarro, Pau %A Ardlie, Kristin %A Balkau, Beverley %A Benediktsson, Rafn %A Bennett, Amanda J %A Blagieva, Roza %A Boerwinkle, Eric %A Bonnycastle, Lori L %A Boström, Kristina Bengtsson %A Bravenboer, Bert %A Bumpstead, Suzannah %A Burtt, Noel P %A Charpentier, Guillaume %A Chines, Peter S %A Cornelis, Marilyn %A Crawford, Gabe %A Doney, Alex S F %A Elliott, Katherine S %A Elliott, Amanda L %A Erdos, Michael R %A Fox, Caroline S %A Franklin, Christopher S %A Ganser, Martha %A Gieger, Christian %A Grarup, Niels %A Green, Todd %A Griffin, Simon %A Groves, Christopher J %A Guiducci, Candace %A Hadjadj, Samy %A Hassanali, Neelam %A Herder, Christian %A Isomaa, Bo %A Jackson, Anne U %A Johnson, Paul R V %A Jørgensen, Torben %A Kao, Wen H L %A Kong, Augustine %A Kraft, Peter %A Kuusisto, Johanna %A Lauritzen, Torsten %A Li, Man %A Lieverse, Aloysius %A Lindgren, Cecilia M %A Lyssenko, Valeriya %A Marre, Michel %A Meitinger, Thomas %A Midthjell, Kristian %A Morken, Mario A %A Narisu, Narisu %A Nilsson, Peter %A Owen, Katharine R %A Payne, Felicity %A Petersen, Ann-Kristin %A Platou, Carl %A Proença, Christine %A Prokopenko, Inga %A Rathmann, Wolfgang %A Rayner, N William %A Robertson, Neil R %A Rocheleau, Ghislain %A Roden, Michael %A Sampson, Michael J %A Saxena, Richa %A Shields, Beverley M %A Shrader, Peter %A Sigurdsson, Gunnar %A Sparsø, Thomas %A Strassburger, Klaus %A Stringham, Heather M %A Sun, Qi %A Swift, Amy J %A Thorand, Barbara %A Tichet, Jean %A Tuomi, Tiinamaija %A van Dam, Rob M %A van Haeften, Timon W %A van Herpt, Thijs %A van Vliet-Ostaptchouk, Jana V %A Walters, G Bragi %A Weedon, Michael N %A Wijmenga, Cisca %A Witteman, Jacqueline %A Bergman, Richard N %A Cauchi, Stephane %A Collins, Francis S %A Gloyn, Anna L %A Gyllensten, Ulf %A Hansen, Torben %A Hide, Winston A %A Hitman, Graham A %A Hofman, Albert %A Hunter, David J %A Hveem, Kristian %A Laakso, Markku %A Morris, Andrew D %A Palmer, Colin N A %A Rudan, Igor %A Sijbrands, Eric %A Stein, Lincoln D %A Tuomilehto, Jaakko %A Uitterlinden, Andre %A Walker, Mark %A Watanabe, Richard M %A Abecasis, Goncalo R %A Boehm, Bernhard O %A Campbell, Harry %A Daly, Mark J %A Hattersley, Andrew T %A Pedersen, Oluf %A Barroso, Inês %A Groop, Leif %A Sladek, Rob %A Thorsteinsdottir, Unnur %A Wilson, James F %A Illig, Thomas %A Froguel, Philippe %A van Duijn, Cornelia M %A Stefansson, Kari %A Altshuler, David %A Boehnke, Michael %A McCarthy, Mark I %A Soranzo, Nicole %A Wheeler, Eleanor %A Glazer, Nicole L %A Bouatia-Naji, Nabila %A Mägi, Reedik %A Randall, Joshua %A Elliott, Paul %A Rybin, Denis %A Dehghan, Abbas %A Hottenga, Jouke Jan %A Song, Kijoung %A Goel, Anuj %A Lajunen, Taina %A Doney, Alex %A Cavalcanti-Proença, Christine %A Kumari, Meena %A Timpson, Nicholas J %A Zabena, Carina %A Ingelsson, Erik %A An, Ping %A O'Connell, Jeffrey %A Luan, Jian'an %A Elliott, Amanda %A McCarroll, Steven A %A Roccasecca, Rosa Maria %A Pattou, François %A Sethupathy, Praveen %A Ariyurek, Yavuz %A Barter, Philip %A Beilby, John P %A Ben-Shlomo, Yoav %A Bergmann, Sven %A Bochud, Murielle %A Bonnefond, Amélie %A Borch-Johnsen, Knut %A Böttcher, Yvonne %A Brunner, Eric %A Bumpstead, Suzannah J %A Chen, Yii-Der Ida %A Chines, Peter %A Clarke, Robert %A Coin, Lachlan J M %A Cooper, Matthew N %A Crisponi, Laura %A Day, Ian N M %A de Geus, Eco J C %A Delplanque, Jerome %A Fedson, Annette C %A Fischer-Rosinsky, Antje %A Forouhi, Nita G %A Franzosi, Maria Grazia %A Galan, Pilar %A Goodarzi, Mark O %A Graessler, Jürgen %A Grundy, Scott %A Gwilliam, Rhian %A Hallmans, Göran %A Hammond, Naomi %A Han, Xijing %A Hartikainen, Anna-Liisa %A Hayward, Caroline %A Heath, Simon C %A Hercberg, Serge %A Hillman, David R %A Hingorani, Aroon D %A Hui, Jennie %A Hung, Joe %A Kaakinen, Marika %A Kaprio, Jaakko %A Kesaniemi, Y Antero %A Kivimaki, Mika %A Knight, Beatrice %A Koskinen, Seppo %A Kovacs, Peter %A Kyvik, Kirsten Ohm %A Lathrop, G Mark %A Lawlor, Debbie A %A Le Bacquer, Olivier %A Lecoeur, Cécile %A Li, Yun %A Mahley, Robert %A Mangino, Massimo %A Martínez-Larrad, María Teresa %A McAteer, Jarred B %A McPherson, Ruth %A Meisinger, Christa %A Melzer, David %A Meyre, David %A Mitchell, Braxton D %A Mukherjee, Sutapa %A Naitza, Silvia %A Neville, Matthew J %A Orrù, Marco %A Pakyz, Ruth %A Paolisso, Giuseppe %A Pattaro, Cristian %A Pearson, Daniel %A Peden, John F %A Pedersen, Nancy L %A Pfeiffer, Andreas F H %A Pichler, Irene %A Polasek, Ozren %A Posthuma, Danielle %A Potter, Simon C %A Pouta, Anneli %A Province, Michael A %A Rayner, Nigel W %A Rice, Kenneth %A Ripatti, Samuli %A Rivadeneira, Fernando %A Rolandsson, Olov %A Sandbaek, Annelli %A Sandhu, Manjinder %A Sanna, Serena %A Sayer, Avan Aihie %A Scheet, Paul %A Seedorf, Udo %A Sharp, Stephen J %A Shields, Beverley %A Sigurðsson, Gunnar %A Sijbrands, Eric J G %A Silveira, Angela %A Simpson, Laila %A Singleton, Andrew %A Smith, Nicholas L %A Sovio, Ulla %A Swift, Amy %A Syddall, Holly %A Syvänen, Ann-Christine %A Tönjes, Anke %A Uitterlinden, André G %A van Dijk, Ko Willems %A Varma, Dhiraj %A Visvikis-Siest, Sophie %A Vitart, Veronique %A Vogelzangs, Nicole %A Waeber, Gérard %A Wagner, Peter J %A Walley, Andrew %A Ward, Kim L %A Watkins, Hugh %A Wild, Sarah H %A Willemsen, Gonneke %A Witteman, Jaqueline C M %A Yarnell, John W G %A Zelenika, Diana %A Zethelius, Björn %A Zhai, Guangju %A Zhao, Jing Hua %A Zillikens, M Carola %A Borecki, Ingrid B %A Meneton, Pierre %A Magnusson, Patrik K E %A Nathan, David M %A Williams, Gordon H %A Silander, Kaisa %A Bornstein, Stefan R %A Schwarz, Peter %A Spranger, Joachim %A Karpe, Fredrik %A Shuldiner, Alan R %A Cooper, Cyrus %A Serrano-Ríos, Manuel %A Lind, Lars %A Palmer, Lyle J %A Hu, Frank B %A Franks, Paul W %A Ebrahim, Shah %A Marmot, Michael %A Kao, W H Linda %A Pramstaller, Peter Paul %A Wright, Alan F %A Stumvoll, Michael %A Hamsten, Anders %A Buchanan, Thomas A %A Valle, Timo T %A Rotter, Jerome I %A Penninx, Brenda W J H %A Boomsma, Dorret I %A Cao, Antonio %A Scuteri, Angelo %A Schlessinger, David %A Uda, Manuela %A Ruokonen, Aimo %A Jarvelin, Marjo-Riitta %A Peltonen, Leena %A Mooser, Vincent %A Sladek, Robert %A Musunuru, Kiran %A Smith, Albert V %A Edmondson, Andrew C %A Stylianou, Ioannis M %A Koseki, Masahiro %A Pirruccello, James P %A Chasman, Daniel I %A Johansen, Christopher T %A Fouchier, Sigrid W %A Peloso, Gina M %A Barbalic, Maja %A Ricketts, Sally L %A Bis, Joshua C %A Feitosa, Mary F %A Orho-Melander, Marju %A Melander, Olle %A Li, Xiaohui %A Li, Mingyao %A Cho, Yoon Shin %A Go, Min Jin %A Kim, Young Jin %A Lee, Jong-Young %A Park, Taesung %A Kim, Kyunga %A Sim, Xueling %A Ong, Rick Twee-Hee %A Croteau-Chonka, Damien C %A Lange, Leslie A %A Smith, Joshua D %A Ziegler, Andreas %A Zhang, Weihua %A Zee, Robert Y L %A Whitfield, John B %A Thompson, John R %A Surakka, Ida %A Spector, Tim D %A Smit, Johannes H %A Sinisalo, Juha %A Scott, James %A Saharinen, Juha %A Sabatti, Chiara %A Rose, Lynda M %A Roberts, Robert %A Rieder, Mark %A Parker, Alex N %A Paré, Guillaume %A O'Donnell, Christopher J %A Nieminen, Markku S %A Nickerson, Deborah A %A Montgomery, Grant W %A McArdle, Wendy %A Masson, David %A Martin, Nicholas G %A Marroni, Fabio %A Lucas, Gavin %A Luben, Robert %A Lokki, Marja-Liisa %A Lettre, Guillaume %A Launer, Lenore J %A Lakatta, Edward G %A Laaksonen, Reijo %A Kyvik, Kirsten O %A König, Inke R %A Khaw, Kay-Tee %A Kaplan, Lee M %A Johansson, Asa %A Janssens, A Cecile J W %A Igl, Wilmar %A Hovingh, G Kees %A Hengstenberg, Christian %A Havulinna, Aki S %A Hastie, Nicholas D %A Harris, Tamara B %A Haritunians, Talin %A Hall, Alistair S %A Groop, Leif C %A Gonzalez, Elena %A Freimer, Nelson B %A Erdmann, Jeanette %A Ejebe, Kenechi G %A Döring, Angela %A Dominiczak, Anna F %A Demissie, Serkalem %A Deloukas, Panagiotis %A de Faire, Ulf %A Crawford, Gabriel %A Chen, Yii-der I %A Caulfield, Mark J %A Boekholdt, S Matthijs %A Assimes, Themistocles L %A Quertermous, Thomas %A Seielstad, Mark %A Wong, Tien Y %A Tai, E-Shyong %A Feranil, Alan B %A Kuzawa, Christopher W %A Taylor, Herman A %A Gabriel, Stacey B %A Holm, Hilma %A Gudnason, Vilmundur %A Krauss, Ronald M %A Ordovas, Jose M %A Munroe, Patricia B %A Kooner, Jaspal S %A Tall, Alan R %A Hegele, Robert A %A Kastelein, John J P %A Schadt, Eric E %A Strachan, David P %A Reilly, Muredach P %A Samani, Nilesh J %A Schunkert, Heribert %A Cupples, L Adrienne %A Sandhu, Manjinder S %A Ridker, Paul M %A Rader, Daniel J %A Kathiresan, Sekar %K Adiponectin %K African Americans %K Asian Continental Ancestry Group %K Cholesterol, HDL %K Diabetes Mellitus, Type 2 %K European Continental Ancestry Group %K Female %K Gene Expression %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Glucose Tolerance Test %K Humans %K Insulin Resistance %K Male %K Metabolic Networks and Pathways %K Polymorphism, Single Nucleotide %K Waist-Hip Ratio %X

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 = 4.5×10(-8)-1.2×10(-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<3×10(-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 = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-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.

%B PLoS Genet %V 8 %P e1002607 %8 2012 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/22479202?dopt=Abstract %R 10.1371/journal.pgen.1002607 %0 Journal Article %J Nat Genet %D 2013 %T Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. %A Berndt, Sonja I %A Gustafsson, Stefan %A Mägi, Reedik %A Ganna, Andrea %A Wheeler, Eleanor %A Feitosa, Mary F %A Justice, Anne E %A Monda, Keri L %A Croteau-Chonka, Damien C %A Day, Felix R %A Esko, Tõnu %A Fall, Tove %A Ferreira, Teresa %A Gentilini, Davide %A Jackson, Anne U %A Luan, Jian'an %A Randall, Joshua C %A Vedantam, Sailaja %A Willer, Cristen J %A Winkler, Thomas W %A Wood, Andrew R %A Workalemahu, Tsegaselassie %A Hu, Yi-Juan %A Lee, Sang Hong %A Liang, Liming %A Lin, Dan-Yu %A Min, Josine L %A Neale, Benjamin M %A Thorleifsson, Gudmar %A Yang, Jian %A Albrecht, Eva %A Amin, Najaf %A Bragg-Gresham, Jennifer L %A Cadby, Gemma %A den Heijer, Martin %A Eklund, Niina %A Fischer, Krista %A Goel, Anuj %A Hottenga, Jouke-Jan %A Huffman, Jennifer E %A Jarick, Ivonne %A Johansson, Asa %A Johnson, Toby %A Kanoni, Stavroula %A Kleber, Marcus E %A König, Inke R %A Kristiansson, Kati %A Kutalik, Zoltán %A Lamina, Claudia %A Lecoeur, Cécile %A Li, Guo %A Mangino, Massimo %A McArdle, Wendy L %A Medina-Gómez, Carolina %A Müller-Nurasyid, Martina %A Ngwa, Julius S %A Nolte, Ilja M %A Paternoster, Lavinia %A Pechlivanis, Sonali %A Perola, Markus %A Peters, Marjolein J %A Preuss, Michael %A Rose, Lynda M %A Shi, Jianxin %A Shungin, Dmitry %A Smith, Albert Vernon %A Strawbridge, Rona J %A Surakka, Ida %A Teumer, Alexander %A Trip, Mieke D %A Tyrer, Jonathan %A van Vliet-Ostaptchouk, Jana V %A Vandenput, Liesbeth %A Waite, Lindsay L %A Zhao, Jing Hua %A Absher, Devin %A Asselbergs, Folkert W %A Atalay, Mustafa %A Attwood, Antony P %A Balmforth, Anthony J %A Basart, Hanneke %A Beilby, John %A Bonnycastle, Lori L %A Brambilla, Paolo %A Bruinenberg, Marcel %A Campbell, Harry %A Chasman, Daniel I %A Chines, Peter S %A Collins, Francis S %A Connell, John M %A Cookson, William O %A de Faire, Ulf %A de Vegt, Femmie %A Dei, Mariano %A Dimitriou, Maria %A Edkins, Sarah %A Estrada, Karol %A Evans, David M %A Farrall, Martin %A Ferrario, Marco M %A Ferrieres, Jean %A Franke, Lude %A Frau, Francesca %A Gejman, Pablo V %A Grallert, Harald %A Grönberg, Henrik %A Gudnason, Vilmundur %A Hall, Alistair S %A Hall, Per %A Hartikainen, Anna-Liisa %A Hayward, Caroline %A Heard-Costa, Nancy L %A Heath, Andrew C %A Hebebrand, Johannes %A Homuth, Georg %A Hu, Frank B %A Hunt, Sarah E %A Hyppönen, Elina %A Iribarren, Carlos %A Jacobs, Kevin B %A Jansson, John-Olov %A Jula, Antti %A Kähönen, Mika %A Kathiresan, Sekar %A Kee, Frank %A Khaw, Kay-Tee %A Kivimaki, Mika %A Koenig, Wolfgang %A Kraja, Aldi T %A Kumari, Meena %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Laitinen, Jaana H %A Lakka, Timo A %A Langenberg, Claudia %A Launer, Lenore J %A Lind, Lars %A Lindström, Jaana %A Liu, Jianjun %A Liuzzi, Antonio %A Lokki, Marja-Liisa %A Lorentzon, Mattias %A Madden, Pamela A %A Magnusson, Patrik K %A Manunta, Paolo %A Marek, Diana %A März, Winfried %A Mateo Leach, Irene %A McKnight, Barbara %A Medland, Sarah E %A Mihailov, Evelin %A Milani, Lili %A Montgomery, Grant W %A Mooser, Vincent %A Mühleisen, Thomas W %A Munroe, Patricia B %A Musk, Arthur W %A Narisu, Narisu %A Navis, Gerjan %A Nicholson, George %A Nohr, Ellen A %A Ong, Ken K %A Oostra, Ben A %A Palmer, Colin N A %A Palotie, Aarno %A Peden, John F %A Pedersen, Nancy %A Peters, Annette %A Polasek, Ozren %A Pouta, Anneli %A Pramstaller, Peter P %A Prokopenko, Inga %A Pütter, Carolin %A Radhakrishnan, Aparna %A Raitakari, Olli %A Rendon, Augusto %A Rivadeneira, Fernando %A Rudan, Igor %A Saaristo, Timo E %A Sambrook, Jennifer G %A Sanders, Alan R %A Sanna, Serena %A Saramies, Jouko %A Schipf, Sabine %A Schreiber, Stefan %A Schunkert, Heribert %A Shin, So-Youn %A Signorini, Stefano %A Sinisalo, Juha %A Skrobek, Boris %A Soranzo, Nicole %A Stančáková, Alena %A Stark, Klaus %A Stephens, Jonathan C %A Stirrups, Kathleen %A Stolk, Ronald P %A Stumvoll, Michael %A Swift, Amy J %A Theodoraki, Eirini V %A Thorand, Barbara %A Trégouët, David-Alexandre %A Tremoli, Elena %A van der Klauw, Melanie M %A van Meurs, Joyce B J %A Vermeulen, Sita H %A Viikari, Jorma %A Virtamo, Jarmo %A Vitart, Veronique %A Waeber, Gérard %A Wang, Zhaoming %A Widen, Elisabeth %A Wild, Sarah H %A Willemsen, Gonneke %A Winkelmann, Bernhard R %A Witteman, Jacqueline C M %A Wolffenbuttel, Bruce H R %A Wong, Andrew %A Wright, Alan F %A Zillikens, M Carola %A Amouyel, Philippe %A Boehm, Bernhard O %A Boerwinkle, Eric %A Boomsma, Dorret I %A Caulfield, Mark J %A Chanock, Stephen J %A Cupples, L Adrienne %A Cusi, Daniele %A Dedoussis, George V %A Erdmann, Jeanette %A Eriksson, Johan G %A Franks, Paul W %A Froguel, Philippe %A Gieger, Christian %A Gyllensten, Ulf %A Hamsten, Anders %A Harris, Tamara B %A Hengstenberg, Christian %A Hicks, Andrew A %A Hingorani, Aroon %A Hinney, Anke %A Hofman, Albert %A Hovingh, Kees G %A Hveem, Kristian %A Illig, Thomas %A Jarvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Keinanen-Kiukaanniemi, Sirkka M %A Kiemeney, Lambertus A %A Kuh, Diana %A Laakso, Markku %A Lehtimäki, Terho %A Levinson, Douglas F %A Martin, Nicholas G %A Metspalu, Andres %A Morris, Andrew D %A Nieminen, Markku S %A Njølstad, Inger %A Ohlsson, Claes %A Oldehinkel, Albertine J %A Ouwehand, Willem H %A Palmer, Lyle J %A Penninx, Brenda %A Power, Chris %A Province, Michael A %A Psaty, Bruce M %A Qi, Lu %A Rauramaa, Rainer %A Ridker, Paul M %A Ripatti, Samuli %A Salomaa, Veikko %A Samani, Nilesh J %A Snieder, Harold %A Sørensen, Thorkild I A %A Spector, Timothy D %A Stefansson, Kari %A Tönjes, Anke %A Tuomilehto, Jaakko %A Uitterlinden, André G %A Uusitupa, Matti %A van der Harst, Pim %A Vollenweider, Peter %A Wallaschofski, Henri %A Wareham, Nicholas J %A Watkins, Hugh %A Wichmann, H-Erich %A Wilson, James F %A Abecasis, Goncalo R %A Assimes, Themistocles L %A Barroso, Inês %A Boehnke, Michael %A Borecki, Ingrid B %A Deloukas, Panos %A Fox, Caroline S %A Frayling, Timothy %A Groop, Leif C %A Haritunian, Talin %A Heid, Iris M %A Hunter, David %A Kaplan, Robert C %A Karpe, Fredrik %A Moffatt, Miriam F %A Mohlke, Karen L %A O'Connell, Jeffrey R %A Pawitan, Yudi %A Schadt, Eric E %A Schlessinger, David %A Steinthorsdottir, Valgerdur %A Strachan, David P %A Thorsteinsdottir, Unnur %A van Duijn, Cornelia M %A Visscher, Peter M %A Di Blasio, Anna Maria %A Hirschhorn, Joel N %A Lindgren, Cecilia M %A Morris, Andrew P %A Meyre, David %A Scherag, Andre %A McCarthy, Mark I %A Speliotes, Elizabeth K %A North, Kari E %A Loos, Ruth J F %A Ingelsson, Erik %K Anthropometry %K Body Height %K Body Mass Index %K Case-Control Studies %K European Continental Ancestry Group %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Genotype %K Humans %K Meta-Analysis as Topic %K Obesity %K Phenotype %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Waist-Hip Ratio %X

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

%B Nat Genet %V 45 %P 501-12 %8 2013 May %G eng %N 5 %1 http://www.ncbi.nlm.nih.gov/pubmed/23563607?dopt=Abstract %R 10.1038/ng.2606 %0 Journal Article %J PLoS Genet %D 2013 %T Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. %A Randall, Joshua C %A Winkler, Thomas W %A Kutalik, Zoltán %A Berndt, Sonja I %A Jackson, Anne U %A Monda, Keri L %A Kilpeläinen, Tuomas O %A Esko, Tõnu %A Mägi, Reedik %A Li, Shengxu %A Workalemahu, Tsegaselassie %A Feitosa, Mary F %A Croteau-Chonka, Damien C %A Day, Felix R %A Fall, Tove %A Ferreira, Teresa %A Gustafsson, Stefan %A Locke, Adam E %A Mathieson, Iain %A Scherag, Andre %A Vedantam, Sailaja %A Wood, Andrew R %A Liang, Liming %A Steinthorsdottir, Valgerdur %A Thorleifsson, Gudmar %A Dermitzakis, Emmanouil T %A Dimas, Antigone S %A Karpe, Fredrik %A Min, Josine L %A Nicholson, George %A Clegg, Deborah J %A Person, Thomas %A Krohn, Jon P %A Bauer, Sabrina %A Buechler, Christa %A Eisinger, Kristina %A Bonnefond, Amélie %A Froguel, Philippe %A Hottenga, Jouke-Jan %A Prokopenko, Inga %A Waite, Lindsay L %A Harris, Tamara B %A Smith, Albert Vernon %A Shuldiner, Alan R %A McArdle, Wendy L %A Caulfield, Mark J %A Munroe, Patricia B %A Grönberg, Henrik %A Chen, Yii-Der Ida %A Li, Guo %A Beckmann, Jacques S %A Johnson, Toby %A Thorsteinsdottir, Unnur %A Teder-Laving, Maris %A Khaw, Kay-Tee %A Wareham, Nicholas J %A Zhao, Jing Hua %A Amin, Najaf %A Oostra, Ben A %A Kraja, Aldi T %A Province, Michael A %A Cupples, L Adrienne %A Heard-Costa, Nancy L %A Kaprio, Jaakko %A Ripatti, Samuli %A Surakka, Ida %A Collins, Francis S %A Saramies, Jouko %A Tuomilehto, Jaakko %A Jula, Antti %A Salomaa, Veikko %A Erdmann, Jeanette %A Hengstenberg, Christian %A Loley, Christina %A Schunkert, Heribert %A Lamina, Claudia %A Wichmann, H Erich %A Albrecht, Eva %A Gieger, Christian %A Hicks, Andrew A %A Johansson, Asa %A Pramstaller, Peter P %A Kathiresan, Sekar %A Speliotes, Elizabeth K %A Penninx, Brenda %A Hartikainen, Anna-Liisa %A Jarvelin, Marjo-Riitta %A Gyllensten, Ulf %A Boomsma, Dorret I %A Campbell, Harry %A Wilson, James F %A Chanock, Stephen J %A Farrall, Martin %A Goel, Anuj %A Medina-Gómez, Carolina %A Rivadeneira, Fernando %A Estrada, Karol %A Uitterlinden, André G %A Hofman, Albert %A Zillikens, M Carola %A den Heijer, Martin %A Kiemeney, Lambertus A %A Maschio, Andrea %A Hall, Per %A Tyrer, Jonathan %A Teumer, Alexander %A Völzke, Henry %A Kovacs, Peter %A Tönjes, Anke %A Mangino, Massimo %A Spector, Tim D %A Hayward, Caroline %A Rudan, Igor %A Hall, Alistair S %A Samani, Nilesh J %A Attwood, Antony Paul %A Sambrook, Jennifer G %A Hung, Joseph %A Palmer, Lyle J %A Lokki, Marja-Liisa %A Sinisalo, Juha %A Boucher, Gabrielle %A Huikuri, Heikki %A Lorentzon, Mattias %A Ohlsson, Claes %A Eklund, Niina %A Eriksson, Johan G %A Barlassina, Cristina %A Rivolta, Carlo %A Nolte, Ilja M %A Snieder, Harold %A van der Klauw, Melanie M %A van Vliet-Ostaptchouk, Jana V %A Gejman, Pablo V %A Shi, Jianxin %A Jacobs, Kevin B %A Wang, Zhaoming %A Bakker, Stephan J L %A Mateo Leach, Irene %A Navis, Gerjan %A van der Harst, Pim %A Martin, Nicholas G %A Medland, Sarah E %A Montgomery, Grant W %A Yang, Jian %A Chasman, Daniel I %A Ridker, Paul M %A Rose, Lynda M %A Lehtimäki, Terho %A Raitakari, Olli %A Absher, Devin %A Iribarren, Carlos %A Basart, Hanneke %A Hovingh, Kees G %A Hyppönen, Elina %A Power, Chris %A Anderson, Denise %A Beilby, John P %A Hui, Jennie %A Jolley, Jennifer %A Sager, Hendrik %A Bornstein, Stefan R %A Schwarz, Peter E H %A Kristiansson, Kati %A Perola, Markus %A Lindström, Jaana %A Swift, Amy J %A Uusitupa, Matti %A Atalay, Mustafa %A Lakka, Timo A %A Rauramaa, Rainer %A Bolton, Jennifer L %A Fowkes, Gerry %A Fraser, Ross M %A Price, Jackie F %A Fischer, Krista %A Krjutå Kov, Kaarel %A Metspalu, Andres %A Mihailov, Evelin %A Langenberg, Claudia %A Luan, Jian'an %A Ong, Ken K %A Chines, Peter S %A Keinanen-Kiukaanniemi, Sirkka M %A Saaristo, Timo E %A Edkins, Sarah %A Franks, Paul W %A Hallmans, Göran %A Shungin, Dmitry %A Morris, Andrew David %A Palmer, Colin N A %A Erbel, Raimund %A Moebus, Susanne %A Nöthen, Markus M %A Pechlivanis, Sonali %A Hveem, Kristian %A Narisu, Narisu %A Hamsten, Anders %A Humphries, Steve E %A Strawbridge, Rona J %A Tremoli, Elena %A Grallert, Harald %A Thorand, Barbara %A Illig, Thomas %A Koenig, Wolfgang %A Müller-Nurasyid, Martina %A Peters, Annette %A Boehm, Bernhard O %A Kleber, Marcus E %A März, Winfried %A Winkelmann, Bernhard R %A Kuusisto, Johanna %A Laakso, Markku %A Arveiler, Dominique %A Cesana, Giancarlo %A Kuulasmaa, Kari %A Virtamo, Jarmo %A Yarnell, John W G %A Kuh, Diana %A Wong, Andrew %A Lind, Lars %A de Faire, Ulf %A Gigante, Bruna %A Magnusson, Patrik K E %A Pedersen, Nancy L %A Dedoussis, George %A Dimitriou, Maria %A Kolovou, Genovefa %A Kanoni, Stavroula %A Stirrups, Kathleen %A Bonnycastle, Lori L %A Njølstad, Inger %A Wilsgaard, Tom %A Ganna, Andrea %A Rehnberg, Emil %A Hingorani, Aroon %A Kivimaki, Mika %A Kumari, Meena %A Assimes, Themistocles L %A Barroso, Inês %A Boehnke, Michael %A Borecki, Ingrid B %A Deloukas, Panos %A Fox, Caroline S %A Frayling, Timothy %A Groop, Leif C %A Haritunians, Talin %A Hunter, David %A Ingelsson, Erik %A Kaplan, Robert %A Mohlke, Karen L %A O'Connell, Jeffrey R %A Schlessinger, David %A Strachan, David P %A Stefansson, Kari %A van Duijn, Cornelia M %A Abecasis, Goncalo R %A McCarthy, Mark I %A Hirschhorn, Joel N %A Qi, Lu %A Loos, Ruth J F %A Lindgren, Cecilia M %A North, Kari E %A Heid, Iris M %K Anthropometry %K Body Height %K Body Mass Index %K Body Weight %K Body Weights and Measures %K Female %K Genetic Loci %K Genome, Human %K Genome-Wide Association Study %K Humans %K Male %K Polymorphism, Single Nucleotide %K Sex Characteristics %K Waist Circumference %K Waist-Hip Ratio %X

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

%B PLoS Genet %V 9 %P e1003500 %8 2013 Jun %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/23754948?dopt=Abstract %R 10.1371/journal.pgen.1003500 %0 Journal Article %J PLoS Genet %D 2013 %T Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained. %A Wu, Ying %A Waite, Lindsay L %A Jackson, Anne U %A Sheu, Wayne H-H %A Buyske, Steven %A Absher, Devin %A Arnett, Donna K %A Boerwinkle, Eric %A Bonnycastle, Lori L %A Carty, Cara L %A Cheng, Iona %A Cochran, Barbara %A Croteau-Chonka, Damien C %A Dumitrescu, Logan %A Eaton, Charles B %A Franceschini, Nora %A Guo, Xiuqing %A Henderson, Brian E %A Hindorff, Lucia A %A Kim, Eric %A Kinnunen, Leena %A Komulainen, Pirjo %A Lee, Wen-Jane %A Le Marchand, Loïc %A Lin, Yi %A Lindström, Jaana %A Lingaas-Holmen, Oddgeir %A Mitchell, Sabrina L %A Narisu, Narisu %A Robinson, Jennifer G %A Schumacher, Fred %A Stančáková, Alena %A Sundvall, Jouko %A Sung, Yun-Ju %A Swift, Amy J %A Wang, Wen-Chang %A Wilkens, Lynne %A Wilsgaard, Tom %A Young, Alicia M %A Adair, Linda S %A Ballantyne, Christie M %A Bůzková, Petra %A Chakravarti, Aravinda %A Collins, Francis S %A Duggan, David %A Feranil, Alan B %A Ho, Low-Tone %A Hung, Yi-Jen %A Hunt, Steven C %A Hveem, Kristian %A Juang, Jyh-Ming J %A Kesäniemi, Antero Y %A Kuusisto, Johanna %A Laakso, Markku %A Lakka, Timo A %A Lee, I-Te %A Leppert, Mark F %A Matise, Tara C %A Moilanen, Leena %A Njølstad, Inger %A Peters, Ulrike %A Quertermous, Thomas %A Rauramaa, Rainer %A Rotter, Jerome I %A Saramies, Jouko %A Tuomilehto, Jaakko %A Uusitupa, Matti %A Wang, Tzung-Dau %A Boehnke, Michael %A Haiman, Christopher A %A Chen, Yii-der I %A Kooperberg, Charles %A Assimes, Themistocles L %A Crawford, Dana C %A Hsiung, Chao A %A North, Kari E %A Mohlke, Karen L %K African Americans %K Apolipoproteins A %K Cholesterol, HDL %K Cholesterol, LDL %K European Continental Ancestry Group %K Genome-Wide Association Study %K Humans %K Lipoproteins, HDL %K Lipoproteins, LDL %K Proprotein Convertases %K Serine Endopeptidases %K Triglycerides %X

Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.

%B PLoS Genet %V 9 %P e1003379 %8 2013 Mar %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/23555291?dopt=Abstract %R 10.1371/journal.pgen.1003379