TY - JOUR
T1 - Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake
AU - Hatchell, Kathryn E.
AU - Lu, Qiongshi
AU - Mares, Julie A.
AU - Michos, Erin D.
AU - Wood, Alexis C.
AU - Engelman, Corinne D.
N1 - Funding Information:
: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute Contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). GENEVA was supported by the National Human Genome Research Institute Grant U01HG004402 (Eric Boerwinkle). The authors would like to thank the staff and participants of the ARIC study for their important contributions. ARIC
Funding Information:
K. E. H. was supported by an NLM training grant to the Computation and Informatics in Biology and Medicine Training Program (NLM 5T15LM007359). Computational resources were supported by a core grant to the Center for Demography and Ecology at the University of Wisconsin‐Madison (P2C HD047873). J. M. was supported by the Department of Ophthalmology and Visual Sciences, and by an unrestricted grant to the Department of Ophthalmology and Visual Sciences from the Research to Prevent Blindness, and by National Institutes of Health, National Eye Institute Grants R01 EY016686 and R01 EY025292. Other:
Funding Information:
MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. MESA was supported by Contracts HHSN268201500003I, N01‐HC‐95159, N01‐HC‐95160, N01‐HC‐95161, N01‐HC‐95162, N01‐HC‐95163, N01‐HC‐95164, N01‐HC‐95165, N01‐HC‐95166, N01‐HC‐95167, N01‐HC‐95168, N01‐HC‐95169, UL1‐TR‐000040, UL1‐TR‐001079, UL1‐TR‐001420, UL1‐TR‐001881, and DK063491. The MESA CARe data used for the analyses described in this study were obtained through Genetics (accession numbers). CARe genotyping was supported by NHLBI Contract N01‐HC‐65226. Vitamin D dataset was supported by Grant HL096875. MESA:
Funding Information:
The WHI program is supported by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and U.S. Department of Health and Human Services through Contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. This study was not prepared in collaboration with investigators of the Women's Health Initiative (WHI), has not been reviewed and/or approved by WHI, and does not necessarily reflect the opinions of the WHI investigators or the NHLBI. WHI PAGE is supported through the NHGRI Population Architecture Using Genomics and Epidemiology (PAGE) network (Grant Number U01 HG004790). Assistance with phenotype harmonization, SNP selection, data cleaning, meta‐analyses, data management and dissemination, and general study coordination was provided by the PAGE Coordinating Center (U01HG004801‐01). WHI GARNET was supported through the NHGRI Genomics and Randomized Trials Network (GARNET; Grant Number U01 HG005152). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GARNET Coordinating Center (U01 HG005157). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard, was provided by the NIH Genes, Environment and Health Initiative (GEI; U01 HG004424). WHI SHARe genotyping was supported by NHLBI Contract N02‐ HL‐64278. WHI:
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 25-Hydroxyvitamin D (25(OH)D) concentration is a complex trait with genetic and environmental predictors that may determine how much vitamin D exposure is required to reach optimal concentration. Interactions between continuous measures of a polygenic score (PGS) and vitamin D intake (PGS*intake) or available ultraviolet (UV) radiation (PGS*UV) were evaluated in individuals of African (n = 1,099) or European (n = 8,569) ancestries. Interaction terms and joint effects (main and interaction terms) were tested using one-degree of freedom (1-DF) and 2-DF models, respectively. Models controlled for age, sex, body mass index, cohort, and dietary intake/available UV. In addition, in participants achieving Institute of Medicine (IOM) vitamin D intake recommendations, 25(OH)D was evaluated by level PGS. The 2-DF PGS*intake, 1-DF PGS*UV, and 2-DF PGS*UV results were statistically significant in participants of European ancestry (p = 3.3 × 10−18, p = 2.1 × 10−2, and p = 2.4 × 10−19, respectively), but not in those of African ancestry. In European-ancestry participants reaching IOM vitamin D intake guidelines, the percent of participants achieving adequate 25(OH)D (>20 ng/ml) increased as genetic risk decreased (72% vs. 89% in highest vs. lowest risk; p =.018). Available UV radiation and vitamin D intake interact with genetics to influence 25(OH)D. Individuals with higher genetic risk may require more vitamin D exposure to maintain optimal 25(OH)D concentrations.
AB - 25-Hydroxyvitamin D (25(OH)D) concentration is a complex trait with genetic and environmental predictors that may determine how much vitamin D exposure is required to reach optimal concentration. Interactions between continuous measures of a polygenic score (PGS) and vitamin D intake (PGS*intake) or available ultraviolet (UV) radiation (PGS*UV) were evaluated in individuals of African (n = 1,099) or European (n = 8,569) ancestries. Interaction terms and joint effects (main and interaction terms) were tested using one-degree of freedom (1-DF) and 2-DF models, respectively. Models controlled for age, sex, body mass index, cohort, and dietary intake/available UV. In addition, in participants achieving Institute of Medicine (IOM) vitamin D intake recommendations, 25(OH)D was evaluated by level PGS. The 2-DF PGS*intake, 1-DF PGS*UV, and 2-DF PGS*UV results were statistically significant in participants of European ancestry (p = 3.3 × 10−18, p = 2.1 × 10−2, and p = 2.4 × 10−19, respectively), but not in those of African ancestry. In European-ancestry participants reaching IOM vitamin D intake guidelines, the percent of participants achieving adequate 25(OH)D (>20 ng/ml) increased as genetic risk decreased (72% vs. 89% in highest vs. lowest risk; p =.018). Available UV radiation and vitamin D intake interact with genetics to influence 25(OH)D. Individuals with higher genetic risk may require more vitamin D exposure to maintain optimal 25(OH)D concentrations.
KW - ancestry-specific
KW - diet
KW - gene–environment interaction
KW - polygenic score
KW - vitamin D
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U2 - 10.1002/gepi.22272
DO - 10.1002/gepi.22272
M3 - Article
C2 - 31830327
AN - SCOPUS:85076406484
SN - 0741-0395
VL - 44
SP - 208
EP - 217
JO - Genetic epidemiology
JF - Genetic epidemiology
IS - 2
ER -