Genetic studies of body mass index yield new insights for obesity biology

• Published in: Nature (London) Vol. 518; no. 7538; pp. 197 - 206
• Main Authors: Croteau-Chonka, Damien C., Wood, Andrew R., Absher, Devin, Bragg-Gresham, Jennifer L., Buyske, Steven, Feitosa, Mary F., Mangino, Massimo, Mateo Leach, Irene, Palmer, Cameron D., Pasko, Dorota, Ju Sung, Yun, Teumer, Alexander, van der Laan, Sander W., Ärnlöv, Johan, Berne, Christian, Bonnycastle, Lori L., Bruinenberg, Marcel, Ida Chen, Yii-Der, de Craen, Anton J. M., Delgado, Graciela, Fraser, Ross M., Grönberg, Henrik, Gusto, Gaëlle, Hassinen, Maija, Jeff, Janina M., Kinnunen, Leena, Kratzer, Wolfgang, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Sin Lo, Ken, Lorbeer, Roberto, Mahajan, Anubha, Milani, Lili, Monda, Keri L., Nolte, Ilja M., Pilz, Stefan, Rettig, Rainer, Ripke, Stephan, Sanna, Serena, Schumacher, Fredrick R., Scott, William R., Smolonska, Joanna, Stirrups, Kathleen, Stringham, Heather M., Uh, Hae-Won, Vandenput, Liesbeth, Warren, Helen R., Brennan, Eoin P., Drong, Alexander W., Min, Josine L., Okada, Yukinori, Takahashi, Atsushi, Tanaka, Toshihiro, Westra, Harm-Jan, Campbell, Harry, den Ruijter, Hester M., Erbel, Raimund, Farrall, Martin, Franco, Oscar H., Gejman, Pablo V., Gieger, Christian, Gottesman, Omri, Hingorani, Aroon D., Hyppönen, Elina, Jarvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Johansen, Berit, Kooperberg, Charles, Langenberg, Claudia, Postma, Dirkje S., Price, Jackie F., Rao, D. C., Rioux, John D., Schunkert, Heribert, Shuldiner, Alan R., Strauch, Konstantin, Tremblay, Angelo, Adair, Linda S., de Bakker, Paul I. W., Ferrucci, Luigi, Hveem, Kristian, März, Winfried, Munroe, Patricia B., Njølstad, Inger, Palmer, Colin N. A., Pedersen, Nancy L., Pérusse, Louis, Saaristo, Timo E., Saleheen, Danish, Sattar, Naveed, Eline Slagboom, P., Tuomilehto, Jaakko, Deloukas, Panos, Stefansson, Kari, van Duijn, Cornelia M., Willer, Cristen J., Ingelsson, Erik, Hirschhorn, Joel N., Loos, Ruth J. F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.02.2015; Nature Publishing Group
• Subjects: 631/208/205/2138; Adipogenesis - genetics; Adiposity - genetics; Age Factors; Biology; Body Mass Index; Central nervous system; Clinical Medicine; Diabetes; Endocrinology and Diabetes; Endokrinologi och diabetes; Energy Metabolism - genetics; Europe - ethnology; Female; Folkhälsovetenskap, global hälsa och socialmedicin; Gene expression; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetic research; Genetics; Genome-Wide Association Study; Genomes; Genomics; Glutamic Acid - metabolism; Health and Welfare; Health aspects; Humanities and Social Sciences; Humans; Hälsa och välfärd; Insulin - metabolism; Insulin Secretion; Klinisk medicin; Male; Medical and Health Sciences; Medical Genetics and Genomics; Medicin och hälsovetenskap; Medicinsk genetik och genomik; Meta-analysis; Metabolic disorders; multidisciplinary; Obesity; Obesity - genetics; Obesity - metabolism; Polymorphism, Single Nucleotide - genetics; Public Health, Global Health and Social Medicine; Quantitative Trait Loci - genetics; Racial Groups - genetics; Science; Studies; Synapses - metabolism; Systematic review; Europe; phenotype; disease course; body mass; gene linkage disequilibrium; genetic association; heredity; gene frequency; genetic variability; insulin release; copy number variation; quantitative trait locus; nonhuman; priority journal; receiver operating characteristic; human; energy metabolism; gene expression; obesity
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature14177

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci ( P  < 5 × 10 −8 ), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis. A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis. Genetic correlates of obesity In the second of two Articles in this issue from the GIANT Consortium, Elizabeth Speliotes and collegues conducted a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), commonly used to define obesity and assess adiposity, to find 97 BMI-associated loci, of which 56 were novel. Many of these loci have significant effects on other metabolic phenotypes. The 97 loci account for about 2.7% of BMI variation, and genome-wide estimates suggest common variation accounts for more than 20% of BMI variation. Pathway analyses implicate the central nervous system in obesity susceptibility including synaptic function, glutamate signaling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.