Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Genetic Architecture of Vitamin D Deficiency Among an Elderly Lebanese Middle Eastern Population: An Exome-wide Association Study

Nagham Nafiz Hindi
ORCID logo ,
Marlene Chakhtoura
ORCID logo ,
Yaser Al-Sarraj
ORCID logo ,
Dania Saleh Bacha
,
Omar Albagha
ORCID logo ,
Ghada El-Hajj Fuleihan
,
Georges Nemer
* ORCID logo
Version 1 : Received: 1 June 2023 / Approved: 8 June 2023 / Online: 8 June 2023 (14:18:18 CEST)

A peer-reviewed article of this Preprint also exists.

Hendi, N.N.; Chakhtoura, M.; Al-Sarraj, Y.; Basha, D.S.; Albagha, O.; Fuleihan, G.E.-H.; Nemer, G. The Genetic Architecture of Vitamin D Deficiency among an Elderly Lebanese Middle Eastern Population: An Exome-Wide Association Study. Nutrients 2023, 15, 3216. Hendi, N.N.; Chakhtoura, M.; Al-Sarraj, Y.; Basha, D.S.; Albagha, O.; Fuleihan, G.E.-H.; Nemer, G. The Genetic Architecture of Vitamin D Deficiency among an Elderly Lebanese Middle Eastern Population: An Exome-Wide Association Study. Nutrients 2023, 15, 3216.

Abstract

Middle East region experiences a high prevalence of hypovitaminosis D, 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 the elderly population, who are more susceptible to health burden. We investigated the genetic determinants of 25-hydroxyvitamin D levels in elderly Lebanese individuals (n=199) through a whole exome-based genome-wide association study. We identified new loci with suggestive evidence of an association with Vitamin D levels, including rs141064014 in the MGAM gene (P-value of 4.40 × 10−06) and rs7036592 in PHF2 (P-value of 8.43 × 10−06). A meta-analysis of the Lebanese data and the largest European genome-wide association study confirmed consistence replication of numerous variants, including rs2725405 in SLC38A10 (P-value of 3.73 x 10-08). Despite the lower performance of European-derived polygenic risk scores compared to the European estimations, it still effectively predicted Vitamin D deficiency among elderly Lebanese individuals. Our findings provide novel insights into the genetic mechanisms of Vitamin D deficiency in Middle Eastern elderly populations, facilitating the development of personalized approaches for more effective management of hypovitaminosis D. Additionally, we demonstrated that whole exome-based genome-wide association study is an effective method for identifying genetic components associated with phenotypes.

Keywords

Exome-wide association stud; Vitamin D deficiency; genetic determinants; polygenic risk score; Middle Eastern population.

Subject

Medicine and Pharmacology, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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