Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Willer, Cristen J.; Speliotes, Elizabeth K.; Loos, Ruth J. F.; Shengxu Li; Lindgren, Cecilia M.; Heid, Iris M.; Berndt, Sonja I.; Elliott, Amanda L.; Jackson, Anne U.; Lamina, Claudia; Lettre, Guillaume; Lim, Noha; Lyon, Helen N.; McCarroll, Steven A.; Papadakis, Konstantinos; Lu Qi; Randall, Joshua C.; Roccasecca, Rosa Maria; Sanna, Serena; Scheet, Paul
January 2009
Nature Genetics;Jan2009, Vol. 41 Issue 1, p25
Academic Journal
Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10−8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.


Related Articles

  • The Morbidity and Mortality Associated With Overweight and Obesity in Adulthood: A Systematic Review. Lenz, Matthias; Richter, Tanja; Mühlhauser, Ingrid // Deutsches Aerzteblatt International;10/2/2009, Vol. 106 Issue 40, p1 

    The article offers information on a study conducted in order to determine the relationship between body mass index (BMI) and morbidity and mortality risks on the basis of international meta-analyses and German population-related cohort studies. The study has revealed that mortality in obese...

  • A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma. Turati, F.; Tramacere, I.; La Vecchia, C.; Negri, E. // Annals of Oncology;Mar2013, Vol. 24 Issue 3, p609 

    Background The incidence rates of esophageal and gastric cardia adenocarcinoma (EGCA) have increased over recent years in several countries, and overweight/obesity has been suggested to play a major role in these trends. In fact, higher body mass index (BMI) has been positively associated with...

  • Implication of European-derived adiposity loci in African Americans. Hester, J M; Wing, M R; Li, J; Palmer, N D; Xu, J; Hicks, P J; Roh, B H; Norris, J M; Wagenknecht, L E; Langefeld, C D; Freedman, B I; Bowden, D W; Ng, M C Y // International Journal of Obesity;Mar2012, Vol. 36 Issue 3, p465 

    Objective:Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity...

  • Meta-Analysis Reveals the Association of Common Variants in the Uncoupling Protein (UCP) 1–3 Genes with Body Mass Index Variability. Brondani, Letícia A.; Assmann, Tais S.; de Souza, Bianca M.; Bouças, Ana P.; Canani, Luis H.; Crispim, Daisy // PLoS ONE;May2014, Vol. 9 Issue 5, p1 

    Background: The relationship between uncoupling protein (UCP) 1–3 polymorphisms and susceptibility to obesity has been investigated in several genetic studies. However, the impact of these polymorphisms on obesity is still under debate, with contradictory results being reported. Until...

  • Diet quality and genetic association with body mass index: results from 3 observational studies. Ding, Ming; Ellervik, Christina; Huang, Tao; Jensen, Majken K; Curhan, Gary C; Pasquale, Louis R; Kang, Jae H; Wiggs, Janey L; Hunter, David J; Willett, Walter C; Rimm, Eric B; Kraft, Peter; Chasman, Daniel I; Qi, Lu; Hu, Frank B; Qi, Qibin // American Journal of Clinical Nutrition;Dec2018, Vol. 108 Issue 6, p1291 

    Background It is unknown whether dietary quality modifies genetic association with body mass index (BMI). Objective This study examined whether dietary quality modifies genetic association with BMI. Design We calculated 3 diet quality scores including the Alternative Healthy Eating Index 2010...

  • The impact of the Catechol-O-methyltransferase Val158Met polymorphism on survival in the general population -- the HUNT study. Hagen, Knut; Stovner, Lars J.; Skorpen, Frank; Pettersen, Elin; Zwart, John-Anker // BMC Medical Genetics;2007, Vol. 8, p1 

    Background: The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met which has been related to common diseases like cancer, psychiatric illness and myocardial infarction. Whether the Val158Met polymorphism is associated with survival has not been evaluated in...

  • Influence of common variants in FTO and near INSIG2 and MC4R on growth curves for adiposity in African- and European-American youth. Liu, Gaifen; Zhu, Haidong; Dong, Yanbin; Podolsky, Robert; Treiber, Frank; Snieder, Harold // European Journal of Epidemiology;Jun2011, Vol. 26 Issue 6, p463 

    Recent genome-wide association (GWA) studies identified several common variants for obesity: rs9939609 in FTO, rs7566605 near INSIG2 and both rs17782313 and rs17700633 near the MC4R gene. This study aimed to assess the influence of these polymorphisms on development of adiposity in European-...

  • Recapitulation of genome-wide association studies on body mass index in the Korean population. Hong, K W; Oh, B // International Journal of Obesity;Aug2012, Vol. 36 Issue 8, p1127 

    Obesity is a risk factor for multiple disorders such as diabetes and cardiovascular disease. Recently, a genome-wide association study for body mass index (BMI) was conducted in 249 796 individuals of European ancestry by the Genetic Investigation of Anthropometric Traits (GIANT) consortium....

  • Identification and Replication of a Novel Obesity Locus on Chromosome 1q24 in Isolated Populations of Cilento. Ciullo, Marina; Nutile, Teresa; Dalmasso, Cyril; Sorice, Rossella; Bellenguez, Céline; Colonna, Vincenza; Persico, Maria Graziella; Bourgain, Catherine // Diabetes;Mar2008, Vol. 57 Issue 3, p783 

    OBJECTIVE--Obesity is a complex trait with a variety of genetic susceptibility variants. Several loci linked to obesity and/or obesity-related traits have been identified, and relatively few regions have been replicated. Studying isolated populations can be a useful approach to identify rare...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics