The Genetic Architecture of Vitamin D Deficiency among an Elderly Lebanese Middle Eastern Population: An Exome-Wide Association Study

Author:

Hendi Nagham Nafiz1ORCID,Chakhtoura Marlene2,Al-Sarraj Yasser3ORCID,Basha Dania Saleh2,Albagha Omar4ORCID,Fuleihan Ghada El-Hajj2,Nemer Georges45ORCID

Affiliation:

1. Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha P.O. Box 34110, Qatar

2. Calcium Metabolism & Osteoporosis Program, American University of Beirut Medical Center, Beirut P.O. Box 11-0236, Lebanon

3. Qatar Genome Program (QGP), Qatar Foundation Research, Development and Innovation, Qatar Foundation (QF), Doha P.O. Box 5825, Qatar

4. Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha P.O. Box 34110, Qatar

5. Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon

Abstract

The Middle East region experiences a high prevalence of vitamin D deficiency, yet most genetic studies on vitamin D have focused on European populations. Furthermore, there is a lack of research on the genomic risk factors affecting elderly people, who are more susceptible to health burdens. We investigated the genetic determinants of 25-hydroxyvitamin D concentrations in elderly Lebanese individuals (n = 199) through a whole-exome-based genome-wide association study. Novel genomic loci displaying suggestive evidence of association with 25-hydroxyvitamin D levels were identified in our study, including rs141064014 in the MGAM (p-value of 4.40 × 10−6) and rs7036592 in PHF2 (p-value of 8.43 × 10−6). A meta-analysis of the Lebanese data and the largest European genome-wide association study confirmed consistency replication of numerous variants, including rs2725405 in SLC38A10 (p-value of 3.73 × 10−8). Although the polygenic risk score model derived from European populations exhibited lower performance than European estimations, it still effectively predicted vitamin D deficiency among our cohort. Our discoveries offer novel perspectives on the genetic mechanisms underlying vitamin D deficiency among elderly Middle Eastern populations, facilitating the development of personalized approaches for more effective management of vitamin D deficiency. Additionally, we demonstrated that whole-exome-based genome-wide association study is an effective method for identifying genetic components associated with phenotypes.

Publisher

MDPI AG

Subject

Food Science,Nutrition and Dietetics

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Pharmacogenomics in Lebanon: current status, challenges and opportunities;The Pharmacogenomics Journal;2024-05-22

2. Genome-Wide Epistatic Network Analyses of Semantic Fluency in Older Adults;International Journal of Molecular Sciences;2024-05-11

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