A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry

Abstract

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations.

Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals

“…To date, 38 BMI-related loci have been identified in GWAS with p<5×10 −8 , of which eight are monomorphic in Han Chinese individuals [1][2][3]. Therefore, a total of 30 BMI-associated SNPs representing independent loci were included in this study.…”

“…We calculated the unweighted GRS of each individual by summing the number of BMI-increasing alleles [1][2][3] of the 30 SNPs. The weighted GRS was calculated by weighting each BMI-increasing allele with the ratio of its reported β-coefficient to the sum of all SNPs' β-coefficients [1][2][3], and summing these values. ; ESM Table 4).…”

“…Genomewide association studies (GWAS) have identified 38 loci convincingly associated with BMI in populations with European, Asian and African ancestry [1][2][3]. Recent studies in Europeans have demonstrated that the genetic susceptibility to obesity leads to increased risk of type 2 diabetes, through its obesity-increasing effect [4].…”

Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies

“…The GIANT Consortium has confirmed 14 known obesity susceptibility loci, and identified 18 new loci associated with BMI (P < 5 × 10 −8 ), bringing the total number of such loci to 32 (3). Subsequently, these 32 loci had been studied by many research groups and then replicated in some studies (4)(5)(6).…”

Joint association analysis of a binary and a quantitative trait in family samples

“…24 Among the remaining top 20 SNVs, chromosome 16 SNVs (rs8059849, rs9931529, rs13332434, rs9783765) are near FTO, a gene known for its association with both BMI and T2D. [24][25][26][27][28][29] The SNV rs10894188 (chromosome 11) is near MTNR1B, a gene known to be associated with both T2D and obesity-related traits; 26 rs12097783 (chromosome 1) is near previously identified BMI gene SEC16B; [29][30][31][32] rs11145958 (chromosome 9) is near GPSM1, a T2D-associated gene; 33 5 SNVs on chromosome 1 are near NOTCH2 25 and ADAM30, 25 two genes known for SNVs associated with T2D; rs17863929 (chromosome 4) is approximately 3 Mb away from IL2, 34 a gene known for SNVs in the intron region associated with type-1 diabetes.…”