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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.

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Figure 1: Manhattan plot showing results of the BMI association meta-analysis in the stage 1 studies.
Figure 2: Regional plots of three new genome-wide significant loci identified in men and women of African ancestry.
Figure 3: Effect estimates (95% confidence intervals) per BMI-increasing allele for the three new loci discovered in individuals of African ancestry (shown in the first section in descending order of the effect size in this population), the 32 loci discovered in individuals of European ancestry (shown in the second section in descending order of their effect size) and the 4 loci discovered in individuals of Asian ancestry (shown in the third section in descending order of their effect size).

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Acknowledgements

A full listing of acknowledgments is detailed in the Supplementary Note.

Author information

Authors and Affiliations

Authors

Consortia

Contributions

Design and/or management of the individual studies: A.A., A.A.A., C.B.A., C.I.A., D.K.A., L.A., M.C.A., M.A.A., S.A., C.H.B., D.M.B., D.W.B., E.P.B., E.V.B., G.B., I.B.B., J.P.B., L.B., S.I.B., W.J.B., C.S.C., G. Casey, G.K.C., J.C., L.C., M.C., N.E.C., Q.C., R.S.C., S.J.C., J.D., P.D., R.W.D., S.L.D.-H., M.K.E., T.L.E., C.F., J.K.F., E.M.G., P.J.G., S.F.A.G., A.H., A.J.M.H., B.E.H., B.V.H., C.A.H., C.C.H., D.H., H.H., K.J.H., J.J.H., J.N.H., V.J.H., S.A.I., E.M.J., J.M.J., C.K., D.L.K., E.A.K., E.K.K., L.N.K., L.H.K., R.A.K., S.J.K., S. Kolb, L.L.M., A.M.L., R.J.F.L., S.L., Yongmei Liu, A.B.M., B.M., K.R.M., R.C.M., T.H.M., J.H.M., J.C.M., I.M.-B., K.E.N., M.C.Y.N., S.N., C.N.-D., U.N., B.N., K.L.N., T.O.O., O.O., O.I.O., B.P., U.P., B.M.P., C.A.P., G.J.P., J.R.P., M.F.P., P.A.P., S.R.P., E.A.R.-N., B.A.R., C.N.R., S.R., J.L.R.-G., A.B.S., A.G.S., J.L.S., L.B.S., P.J.S., S.B.S., S.W.-S., M.R.S., M.M.S., I.J.S., S.S.S., H.T., M.J.T., M.A.T., M.V., J.S.W., X.W., J.K.W., S.M.W., L.K.W., M.W., J.J.Y., N.A.Z., R.G.Z., W. Zheng, A.B.Z., K.A.Z., Y.Z. and X.Z.

Genotyping: A.B., U.B., S.J.C., Y.-D.I.C., D.D., T.L.E., S.F.A.G., X.G., D.G.H., J.N.H., T.D.H., T. Haritunians, K.C.J., Yongmei Liu, Y. Lu, W.M., R.N., J.R.P., N.D.P., S.B.S. and D.J.V.D.B.

Phenotyping: A.A.A., D.K.A., M.A.A., E.P.B., R.S.C., E.D., B.I.F., O.G., S.F.A.G., J.N.H., T. Haritunians, K.C.J., A.K., C.K., E.K.K., S.L., J.E.M., M.N., R.N., A.O., H.O.-B., B.M.P., J.R.P., S.R.P., C.N.R., E.R., S.R., B.S., D.S., L.S., B.O.T. and T.R.Y.

Statistical methods and data analysis: A.A.A., D.K.A., L.F.B., C.W.K.C., G.K.C., G. Casey, N.E.C., W.-M.C., G.A.C., Y.-D.I.C., J.D., P.D., T.L.E., C.F., M.F.F., J.P.B., E.M.G., M.G., O.G., X.G., C.A.H., M.R.I., A.K., B.J.K., C.K., E.K.K., S.J.K., C.D.L., G. Lettre, G. Li, H.L., K.L., L.A.L., R.J.F.L., V.L., Yongmei Liu, Youfang Liu, Y. Lu, B.M., K.L.M., Y.A.M., A.N., K.E.N., M.A.N., M.C.Y.N., C.P., J.R.P., E.A.R.-N., S.K.R., B.P., A.P.R., L.J.R.-T., D.A.S., E.K.S., E.E.S., Y.V.S., B.O.T., K.C.T., D.R.V.E., M.K.W., Z.W., L.K.W., T.W.W., L.R.Y., J.Z., J.H.Z., N.A.Z., J.M.Z., W. Zhao, the NABEC Consortium, the UKBEC Consortium, the BioBank Japan Project and the AGEN Consortium.

Writing group: G.K.C., T.L.E., M.G., B.E.H., J.N.H., R.J.F.L., C.A.H., L.A.L., K.L.M., K.E.N., M.C.Y.N., C.P., G.J.P., A.P.R. and K.C.T.

Critical review of the manuscript: A.A.A., A.A., C.B.A., C.I.A., D.K.A., L.A., M.A.A., M.C.A., S.A., A.B., C.H.B., D.M.B., D.W.B., E.P.B., E.V.B., G.B., I.B.B., J.P.B., L.F.B., L.B., S.I.B., U.B., W.J.B., C.W.K.C., C.S.C., F.C., G.A.C., G.K.C., G. Casey, G. Chen, J.C., L.C., M.C., N.E.C., Q.C., R.S.C., S.J.C., W.-M.C., Y.-D.I.C., D.D., E.D., J.D., P.D., R.W.D., S.L.D.-H., M.K.E., T.L.E., C.F., J.K.F., M.F.F., B.I.F., Y.F., E.M.G., G.S.G., M.G., O.G., P.J.G., S.F.A.G., W.T.G., X.G., A.J.M.H., A.H., B.E.H., B.V.H., C.A.H., C.C.H., D.G.H., D.H., H.H., J.J.H., J.N.H., K.J.H., T.D.H., T. Haritunians, T. Harris, V.J.H., J.H.M., M.R.I., S.A.I., E.M.J., J.M.J., K.C.J., A.K., B.J.K., C.K., D.L.K., E.A.K., E.K.K., L.N.K., L.H.K., R.A.K., S.J.K., S.L.R.K., S. Kolb, S. Ketkar, A.M.L., C.D.L., G. Lettre, G. Li, H.L., K.L., L.A.L., L.L., M.C.L., R.J.F.L., S.L., V.L., Yongmei Liu, Youfang Liu, Y. Lu, A.B.M., B.M., J.C.M., J.E.M., L.H.M., K.L.M., K.R.M., R.C.M., T.H.M., W.M., Y.A.M., I.M.-B., A.N., B.N., K.E.N., K.L.N., M.A.N., M.C.Y.N., M.N., R.N., S.N., U.N., C.N.-D., O.I.O., O.O., T.O.O., A.O., H.O.-B., B.M.P., B.P., C.A.P., C.P., G.J.P., J.R.P., M.F.P., N.D.P., P.A.P., S.R.P., U.P., A.P.R., B.A.R., C.N.R., E.R., S.K.R., S.R., J.L.R.-G., E.A.R.-N., L.J.R.-T., A.B.S., A.G.S., B.S., D.A.S., D.S., E.K.S., E.E.S., I.J.S., J.L.S., L.B.S., L.S., M.M.S., M.R.S., P.J.S., S.B.S., S.S.S., Y.V.S., B.O.T., K.C.T., M.A.T., H.T., M.J.T., M.V., D.J.V.D.B., D.R.V.E., J.K.W., M.W., S.M.W., S.-Y.W., S.W.-S., T.W.W., X.W., Z.W., L.K.W., J.S.W., M.K.W., J.J.Y., L.R.Y., T.R.Y., A.B.Z., J.Z., J.M.Z., J.H.Z., K.A.Z., N.A.Z., R.G.Z., W. Zhao, W Zheng, X.Z. and Y.Z.

Corresponding authors

Correspondence to Kari E North or Christopher A Haiman.

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The authors declare no competing financial interests.

Additional information

A list of contributing members appears in the Supplementary Note.

A list of contributing members appears in the Supplementary Note.

A list of contributing members appears in the Supplementary Note.

A list of contributing members appears in the Supplementary Note.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1–18, Supplementary Figures 1–9 and Supplementary Note (PDF 7576 kb)

Supplementary Table 19

Comprehensive results of the biofeature analysis for the three novel loci (XLS 190 kb)

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Monda, K., Chen, G., Taylor, K. et al. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 45, 690–696 (2013). https://doi.org/10.1038/ng.2608

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