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 new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included 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 showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which 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.

Figure 1

Manhattan plot displaying results of the BMI association meta-analysis in the Stage 1 studies. Colored genomic loci indicate novel associations (red) and those detected previously (blue).

Figure 2

Regional plots of three novel genome-wide significant loci identified in men and women of African ancestry. (a) rs7708584 (GALNT10 region), (b) rs974417 (KLHL32 region), and (c) rs10261878 (MIR148A/NFE2L3 region). For 2a and b, Stage 1 p-value represented by purple circle and Stage 1+2+3 p-value represented by purple square; for 2c, Stage 1 p-value represented by purple circle, African ancestry Stage 1+2+3 p-value represented by purple diamond, and African ancestry + GIANT p-value represented by purple square. SNPs are plotted by their position 500kb on either side of the index SNP on the chromosome against their association (−log₁₀ P) with BMI using the Stage 1 data. SNPs surrounding the top SNPs are colored to indicate the local LD structure using pairwise r² data from the May 2012 AFR panel of the 1000 genomes.

Figure 2

Regional plots of three novel genome-wide significant loci identified in men and women of African ancestry. (a) rs7708584 (GALNT10 region), (b) rs974417 (KLHL32 region), and (c) rs10261878 (MIR148A/NFE2L3 region). For 2a and b, Stage 1 p-value represented by purple circle and Stage 1+2+3 p-value represented by purple square; for 2c, Stage 1 p-value represented by purple circle, African ancestry Stage 1+2+3 p-value represented by purple diamond, and African ancestry + GIANT p-value represented by purple square. SNPs are plotted by their position 500kb on either side of the index SNP on the chromosome against their association (−log₁₀ P) with BMI using the Stage 1 data. SNPs surrounding the top SNPs are colored to indicate the local LD structure using pairwise r² data from the May 2012 AFR panel of the 1000 genomes.

Figure 2

Regional plots of three novel genome-wide significant loci identified in men and women of African ancestry. (a) rs7708584 (GALNT10 region), (b) rs974417 (KLHL32 region), and (c) rs10261878 (MIR148A/NFE2L3 region). For 2a and b, Stage 1 p-value represented by purple circle and Stage 1+2+3 p-value represented by purple square; for 2c, Stage 1 p-value represented by purple circle, African ancestry Stage 1+2+3 p-value represented by purple diamond, and African ancestry + GIANT p-value represented by purple square. SNPs are plotted by their position 500kb on either side of the index SNP on the chromosome against their association (−log₁₀ P) with BMI using the Stage 1 data. SNPs surrounding the top SNPs are colored to indicate the local LD structure using pairwise r² data from the May 2012 AFR panel of the 1000 genomes.

Figure 3

Effect estimates (95% CI) per BMI-increasing allele for the 3 novel loci discovered in individuals of African ancestry (1^st section, in descending order of African effect size), the 32 loci discovered in individuals of European ancestry (2^nd section, in descending order of European effect size), and the 4 loci discovered in individuals of Asian ancestry (3^rd section, in descending order of Asian effect size). Results for individuals of African ancestry depicted by red dots (Stage 1+2+3 for novel loci, Stage 1 for previously-discovered loci); results for individuals of European ancestry depicted by black squares from Speliotes EK et al, 2010; and results for individuals of Asian ancestry depicted by green triangles from Okada Y et al, 2012 and Wen W et al, 2012.