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

By Cristen J. Willer, Elizabeth K. Speliotes, Ruth J. F. Loos, Shengxu Li, C. Lindgren, I. Heid, S. Berndt, A. Elliott, A. Jackson, C. Lamina and 135 more. Nature Genetics, 2008

1,801 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Endocrine and Autonomic Systems, Genetics

View Paper: https://www.semanticscholar.org/paper/e66d21b29dff35f618014e54d3cbf5362f11249b

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Citations in the corpus

MaCH: Using Sequence and Genotype Data to Estimate Haplotypes and Unobserved Genotypes (2010, background): “…and a subset of the loci with smaller effect [Hirschhorn and Daly, 2005], many alleles that contribute to complex disease can only be identified through the meta-analysis of multiple genome-wide scans [for specific examples, see Lettre et al., 2008; Sanna et al., 2008; Willer et al., 2008, 2009].”
The Rotterdam Study: 2010 objectives and design update (2007, background): “Especially, from the CHARGE consortium (the Rotterdam Study together with the Framingham Study, AGES, CHS, and ARIC) many important publications have emerged on a wide variety of phenotypes and diseases from all major research lines in the Rotterdam Study [288–292].”
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution (2010, neutral): “Of the ten loci shown to be associated with BMI in previous GWAS 14 , 15 , 18 , only two showed nominally significant ( P < 0.05) associations for BMI-adjusted WHR in the discovery analysis ( FTO , rs8050136, P = 0.03, n = 77,074; TMEM18 , rs6548238, P = 3.0 × 10 − 3 , n = 77,016).”
Metabolism Disrupting Chemicals and Metabolic Disorders (2016, neutral): “Three SNPs are significantly related to obesity: one in FTO (fat mass and the obesity-associated gene), one near TMEM18 (transmembrane protein 18) and one near MC4R (melatocortin 4 receptor) [29, 34-36].”
Variability in the Heritability of Body Mass Index: A Systematic Review and Meta-Regression (2012, background): “Genome-wide association studies (GWAS) have so far identified 32 loci robustly associated with adult BMI (Frayling et al., 2007; Loos et al., 2008; Thorleifsson et al., 2009; Willer et al., 2009; Speliotes et al., 2010).”
METAL: fast and efficient meta-analysis of genomewide association scans (2010, methodology): “Availability and implementation: METAL, including source code, documentation, examples, and executables, is available at http:// www.sph.umich.edu/csg/abecasis/metal/ Contact: goncalo@umich.edu Received on April 15, 2010; revised on June 17, 2010; accepted on June 18, 2010”