Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration

IF 1 4区 医学 Q4 GENETICS & HEREDITY
Hailey A. Kresge, Freida Blostein, Slavina Goleva, Clara Albiñana, Joana A. Revez, Naomi R. Wray, Bjarni J. Vilhjálmsson, Zhihong Zhu, John J. McGrath, Lea K. Davis
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Abstract

While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.
与 25 羟基维生素 D 浓度和维生素 D 结合蛋白浓度的遗传相关性有关的健康结果的全基因组关联研究
众所周知,维生素 D 缺乏与不良骨质结果有关,但低维生素 D 状态是否会增加更多健康结果的风险,目前仍不清楚。我们有机会在一个大型学术医疗中心探索与 25 羟基维生素 D(25OHD)和维生素 D 结合蛋白(DBP,由 GC 基因编码)相关的常见遗传变异与一系列健康疾病和实验室检测之间的关联。我们使用 25OHD 和 DBP 的汇总统计数据,为范德比尔特大学医学中心生物库 (BioVU) 的 66,482 名主要为欧洲血统的参与者和 13,285 名主要为非洲血统的参与者生成了多基因评分 (PGS)。我们研究了 PGS25OHD 和两个与 DBP 浓度相关的评分对电子健康记录中 1322 种健康相关表型和 315 种实验室测量表型的预测特性。在欧洲血统的人群中:(a) PGS25OHD 和 PGSDBP 评分以及单个 SNPs rs4588 和 rs7041 与 25OHD 浓度和 1,25 二羟维生素 D 浓度相关;(b) PGS25OHD 越高,甘油三酯和胆固醇浓度越低,维生素 D 缺乏症、脂代谢紊乱和糖尿病的风险也越低。总体而言,非洲血统组的研究结果与欧洲血统组的分析结果一致。我们的研究证实了 PGS 和 GC 基因中的两个关键变异(rs4588 和 rs7041)在临床环境中预测维生素 D 缺乏风险的实用性,并强调了维生素 D 相关遗传途径与一系列健康结果之间的共同生物学特性。
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来源期刊
Twin Research and Human Genetics
Twin Research and Human Genetics 医学-妇产科学
CiteScore
1.50
自引率
11.10%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Twin Research and Human Genetics is the official journal of the International Society for Twin Studies. Twin Research and Human Genetics covers all areas of human genetics with an emphasis on twin studies, genetic epidemiology, psychiatric and behavioral genetics, and research on multiple births in the fields of epidemiology, genetics, endocrinology, fetal pathology, obstetrics and pediatrics. Through Twin Research and Human Genetics the society aims to publish the latest research developments in twin studies throughout the world.
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