Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study

Author:

Palmer Nicholette D.ORCID,Lu Lingyi,Register Thomas C.,Lenchik Leon,Carr J. Jeffrey,Hicks Pamela J.,Smith S. Carrie,Xu Jianzhao,Dimitrov Latchezar,Keaton Jacob,Guan Meijian,Ng Maggie C. Y.,Chen Yii-der I.,Hanley Anthony J.,Engelman Corinne D.,Norris Jill M.,Langefeld Carl D.,Wagenknecht Lynne E.,Bowden Donald W.,Freedman Barry I.,Divers Jasmin

Abstract

Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic plaque (subclinical atherosclerosis). To identify genetic factors contributing to vitamin D and BMD measures, association analysis of >14M variants was conducted in a maximum of 697 African American-Diabetes Heart Study participants with type 2 diabetes (T2D). The most significant association signals were detected for VDBP on chromosome 4; variants rs7041 (β = 0.44, SE = 0.019, P = 9.4x10-86) and rs4588 (β = 0.17, SE = 0.021, P = 3.5x10-08) in the group-specific component (vitamin D binding protein) gene (GC). These variants were found to be independently associated. In addition, rs7041 was also associated with bioavailable vitamin D (BAVD; β = 0.16, SE = 0.02, P = 3.3x10-19). Six rare variants were significantly associated with 25OHD, including a non-synonymous variant in HSPG2 (rs116788687; β = -1.07, SE = 0.17, P = 2.2x10-10) and an intronic variant in TNIK (rs143555701; β = -1.01, SE = 0.18, P = 9.0x10-10), both biologically related to bone development. Variants associated with 25OHD failed to replicate in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of vitamin D metabolism and bone mineral density phenotypes in an African American population enriched for T2D could provide insight into ethnic specific differences in vitamin D metabolism and bone mineral density.

Funder

National Institute on Aging

National Institute of Diabetes and Digestive and Kidney Diseases

National Heart, Lung, and Blood Institute

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

Reference42 articles.

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