Genome-Wide Association Study of Serum 25-Hydroxyvitamin D in US Women
O'Brien KM, Sandler DP, Shi M, Harmon QE, Taylor JA, Weinberg CR
Frontiers in genetics · 32 citations
How it was studied
- Design
- Cohort study (classified by our AI screen)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- Office of Dietary Supplements
- Government
- National Institutes of Health
- Government
- Intramural NIH HHS
- Grants
- National Institutes of Health (Z01-ES102245); National Institutes of Health (Z01 ES049033); National Institutes of Health (Z01‐ES044005)
Based on 3 listed funder(s).
Publication
- Published
- 2018-03-01 · Front Genet · vol. 9 · p. 67
- Publisher
- Frontiers Media
- Cited
- 43 citations · more than 94% of similar papers · 3.7× the field average
- Impact
- Top 10% most cited in its field
- References
- 58 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Vitamin D Research Studies · Nutrition, Genetics, and Disease
- Keywords
- Single-nucleotide polymorphism, Vitamin D and neurology, Minor allele frequency, Vitamin D-binding protein, Breast cancer, vitamin D deficiency, Internal medicine, Genetics, Biology, Medicine, Genotype, Cancer, Gene
6 authors
From US
- Katie M. O’Brien · correspondingNational Institute of Environmental Health Sciences
- Dale P. SandlerNational Institute of Environmental Health Sciences
- Min ShiNational Institute of Environmental Health Sciences
- Quaker E. HarmonNational Institute of Environmental Health Sciences
- Jack A. TaylorNational Institute of Environmental Health Sciences
- Clarice Ring WeinbergNational Institute of Environmental Health Sciences
Abstract
Genetic factors likely influence individuals' concentrations of 25-hydroxyvitamin D [25(OH)D], a biomarker of vitamin D exposure previously linked to reduced risk of several chronic diseases. We conducted a genome-wide association study of serum 25(OH)D (assessed using liquid chromatography-tandem mass spectrometry) and 386,449 single nucleotide polymorphisms (SNPs). Our sample consisted of 1,829 participants randomly selected from the Sister Study, a cohort of women who had a sister with breast cancer but had never had breast cancer themselves. 19,741 SNPs were associated with 25(OH)D (p p -8). These were located in or near GC, the vitamin D binding protein, or CYP2R1, a cytochrome P450 enzyme that hydroxylates vitamin D to form 25(OH)D. The top hit was rs4588, a missense GC polymorphism associated with a 3.5 ng/mL decrease in 25(OH)D per copy of the minor allele (95% confidence interval [CI]: -4.1, -3.0; p = 4.5 × 10-38). The strongest SNP near CYP2R1 was rs12794714, a synonymous variant (p = 3.8 × 10-12; β = 1.8 ng/mL decrease in 25(OH)D per minor allele [CI: -2.2, -1.3]). Serum 25(OH)D concentrations from samples collected from some participants 3-10 years after baseline (811 cases, 780 non-cases) were also strongly associated with both loci. These findings augment our understanding of genetic influences on 25(OH)D and the possible role of vitamin D binding proteins and cytochrome P450 enzymes in determining measured levels. These results may help to identify individuals genetically predisposed to vitamin D insufficiency.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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