Meta-analysis identifies common variants associated with body mass index in east Asians

Abstract

Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We conducted a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 East Asians, followed by in silico and de novo replication in 37,691 and 17,642 additional East Asians, respectively. We identified ten BMI-associated loci at the genome-wide significance level (P<5.0×10−8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR/QPCTL, ADCY3/RBJ, BDNF, and MAP2K5) and three novel loci in or near the CDKAL1,PCSK1, and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a new locus near PAX6, which all had P<5.0×10−7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.

Strong influence of dietary intake and physical activity on body fatness in elderly Japanese men: age-associated loss of polygenic resistance against obesity

“…All selected SNPs met the following criteria: (1) a significant genome-wide association (p \ 5.0 9 10 -8 ) in any GWAS of European-descent populations (Thorleifsson et al 2009;Willer et al 2009), (2) a suggestive association (p \ 1.0 9 10 -4 ) in the meta-analysis in Asian populations (Wen et al 2012), and (3) the minor allele frequency (MAF) in the Japanese population was C0.05. SEC16B rs574367, TMEM18 rs11127485, TFAP2B rs4715210, and MC4R rs6567160 were not included in the SNP array in the present study; these were replaced with rs543874, rs2867125, rs987237, and rs10871777, all of which are in strong linkage disequilibrium with the original SNPs, respectively (D 0 = 1.0, r 2 [ 0.7, in HapMap JPN).…”

“…We assumed that each SNP acts in an additive manner, and the GRS was calculated using a weighted method (Cheung et al 2010;Renstrom et al 2009;Tanisawa et al 2014). Each SNP was weighted by its effect size per allele on BMI (in percentage of the SD) derived from a meta-analysis in Asian populations (Wen et al 2012). The weighted scores for each SNP were calculated by multiplying each effect size by the number of corresponding risk alleles.…”

“…Recent genome-wide association studies (GWASs) identified single nucleotide polymorphisms (SNPs) at several genetic loci that are associated with BMI in European and Asian populations (Thorleifsson et al 2009;Wen et al 2012;Willer et al 2009). Several studies calculated the genetic risk score (GRS) from the number of risk alleles of GWAS-derived SNPs to examine the polygenic effect of these variants and demonstrated that the GRS is strongly associated with BMI (Cheung et al 2010;Peterson et al 2011;Renstrom et al 2009).…”

Associations of obesity susceptibility loci with hypertension in Chinese children

“…13 However, the FTO-type 2 diabetes association disappeared after adjustment for BMI, suggesting the effect of FTO locus on type 2 diabetes was completely mediated by BMI. 13 Then, the FTO locus was considered as the first gene for common obesity. Since then, other SNPs in/near the MC4R, GNPDA2, BDNF, FAIM2, NPC1, SEC16B, SH2B1, PCSK1, KCTD15 and BAT2 have emerged.…”

“…13,14 Interestingly, the fat mass and obesity-associated (FTO) locus was initially reported as the type 2 diabetes susceptibility gene by the GWAS. 13 However, the FTO-type 2 diabetes association disappeared after adjustment for BMI, suggesting the effect of FTO locus on type 2 diabetes was completely mediated by BMI. 13 Then, the FTO locus was considered as the first gene for common obesity.…”