In:
Endocrinology and Metabolism, Korean Endocrine Society, Vol. 36, No. 6 ( 2021-12-31), p. 1189-1200
Abstract:
Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.Results: rs12803256, in the actin epsilon 1, pseudogene ( 〈 i 〉 ACTE1P 〈 /i 〉 ) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B ( 〈 i 〉 PDE3B 〈 /i 〉 ) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase ( 〈 i 〉 NADSYN1 〈 /i 〉 ) and 7-dehydrocholesterol reductase ( 〈 i 〉 DHCR7 〈 /i 〉 ), showed significantly different expression according to alleles.Conclusion: The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, 〈 i 〉 PDE3B 〈 /i 〉 , 〈 i 〉 NADSYN1 〈 /i 〉 , and 〈 i 〉 ACTE1P 〈 /i 〉 genes. The biological mechanism of a non-coding SNP (rs12803256) for 〈 i 〉 DHCR7 〈 /i 〉 / 〈 i 〉 NADSYN1 〈 /i 〉 on vitamin D concentrations is unclear, warranting further investigations.
Type of Medium:
Online Resource
ISSN:
2093-596X
,
2093-5978
DOI:
10.3803/EnM.2021.1241
Language:
English
Publisher:
Korean Endocrine Society
Publication Date:
2021
detail.hit.zdb_id:
2802452-7
