The genetics of vitamin D

Created January 2020

Bone 126 (2019) 59-77

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Heritability

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Xia Jianga,b’*, Douglas P. Kiel' -'1-6, Peter Kraft3

a Program in Genetic Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Brookline, Boston 02115, USA

b Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Nobels vagen 13, Stockholm 17177, Sweden

c Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA 02131, United States

d Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, United States

e Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, MA 02142, United States

Vitamin D plays an essential role in human health as it influences immune function, cell proliferation, differentiation and apoptosis. Vitamin D deficiency has been associated with numerous health outcomes, including bone disease, cancer, autoimmune disease, cardiovascular conditions and more. However, the causal role of vitamin D beyond its importance for bone health remains unclear and is under much debate.

Twin and familial studies from past decades have demonstrated a nontrivial heritability of circulating vitamin D concentrations.

Several large-scale genome-wide association studies (GWAS) have discovered associations of GC, NADSYN1/ DHCR7, CYP2R1, CYP24A1, SEC23A, AMDHD1 with serum levels of vitamin D. A recent whole genome sequencing (WGS) study, combined with deep imputation of genome-wide genotyping, has identified a low-frequency synonymous coding variant at CYP2R1. Information on these genetic variants can be used as tools for downstream analysis such as Mendelian randomization. Here, we review the genetic determinants of circulating vitamin D levels by focusing on new findings from GWAS and WGS, as well as results from Mendelian randomization analyses conducted so far for vitamin D with various traits and diseases. The amount of variation in vitamin D explained by genetics is still small , and the putative causal relationship between vitamin D and other diseases remains to be demonstrated.

Tags: Genetics