Open AccessAncestry-specific polygenic scores and SNP heritability of 25(OH)D in African- and European-ancestry populations
Author(s) -
Kathryn E. Hatchell,
Qiongshi Lu,
Scott J. Hebbring,
Erin D. Michos,
Alexis C. FrazierWood,
Corinne D. Engelman
Publication year - 2019
Publication title -
human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.351
H-Index - 137
eISSN - 1432-1203
pISSN - 0340-6717
DOI - 10.1007/s00439-019-02049-x
Subject(s) - genome wide association study , genetic genealogy , heritability , biology , single nucleotide polymorphism , vitamin d and neurology , cohort , genetic association , demography , snp , genetics , ancestry informative marker , population , genotype , medicine , gene , endocrinology , sociology
Vitamin D inadequacy, assessed by 25-hydroxyvitamin D [25(OH)D], affects around 50% of adults in the United States and is associated with numerous adverse health outcomes. Blood 25(OH)D concentrations are influenced by genetic factors that may determine how much vitamin D intake is required to reach optimal 25(OH)D. Despite large genome-wide association studies (GWASs), only a small portion of the genetic factors contributing to differences in 25(OH)D has been discovered. Therefore, knowledge of a fuller set of genetic factors could be useful for risk prediction of 25(OH)D inadequacy, personalized vitamin D supplementation, and prevention of downstream morbidity and mortality. Using PRSice and weights from published African- and European-ancestry GWAS summary statistics, ancestry-specific polygenic scores (PGSs) were created to capture a more complete set of genetic factors in those of European (n = 9569) or African ancestry (n = 2761) from three cohort studies. The PGS for African ancestry was derived using all input SNPs (a p value cutoff of 1.0) and had an R 2 of 0.3%; for European ancestry, the optimal PGS used a p value cutoff of 3.5 × 10 -4 in the target/tuning dataset and had an R 2 of 1.0% in the validation cohort. Those with highest genetic risk had 25(OH)D that was 2.8-3.0 ng/mL lower than those with lowest genetic risk (p = 0.0463-3.2 × 10 -13 ), requiring an additional 467-500 IU of vitamin D intake to maintain equivalent 25(OH)D. PGSs are a powerful predictive tool that could be leveraged for personalized vitamin D supplementation to prevent the negative downstream effects of 25(OH)D inadequacy.