Genome-wide landscape establishes novel association signals for metabolic traits in the Arab population
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ORIGINAL INVESTIGATION
Genome‑wide landscape establishes novel association signals for metabolic traits in the Arab population Prashantha Hebbar1,2 · Jehad Ahmed Abubaker1 · Mohamed Abu‑Farha1 · Osama Alsmadi3 · Naser Elkum4 · Fadi Alkayal1 · Sumi Elsa John1 · Arshad Channanath1 · Rasheeba Iqbal1 · Janne Pitkaniemi5 · Jaakko Tuomilehto5,6 · Robert Sladek7 · Fahd Al‑Mulla1 · Thangavel Alphonse Thanaraj1 Received: 26 February 2020 / Accepted: 1 September 2020 © The Author(s) 2020
Abstract While the Arabian population has a high prevalence of metabolic disorders, it has not been included in global studies that identify genetic risk loci for metabolic traits. Determining the transferability of such largely Euro-centric established risk loci is essential to transfer the research tools/resources, and drug targets generated by global studies to a broad range of ethnic populations. Further, consideration of populations such as Arabs, that are characterized by consanguinity and a high level of inbreeding, can lead to identification of novel risk loci. We imputed published GWAS data from two Kuwaiti Arab cohorts (n = 1434 and 1298) to the 1000 Genomes Project haplotypes and performed meta-analysis for associations with 13 metabolic traits. We compared the observed association signals with those established for metabolic traits. Our study highlighted 70 variants from 9 different genes, some of which have established links to metabolic disorders. By relaxing the genome-wide significance threshold, we identified ‘novel’ risk variants from 11 genes for metabolic traits. Many novel risk variant association signals were observed at or borderline to genome-wide significance. Furthermore, 349 previously established variants from 187 genes were validated in our study. Pleiotropic effect of risk variants on multiple metabolic traits were observed. Fine-mapping illuminated rs7838666/CSMD1 rs1864163/CETP and rs112861901/[INTS10,LPL] as candidate causal variants influencing fasting plasma glucose and high-density lipoprotein levels. Computational functional analysis identified a variety of gene regulatory signals around several variants. This study enlarges the population ancestry diversity of available GWAS and elucidates new variants in an ethnic group burdened with metabolic disorders. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00439-020-02222-7) contains supplementary material, which is available to authorized users. * Fahd Al‑Mulla [email protected] * Thangavel Alphonse Thanaraj [email protected] 1
Dasman Diabetes Institute, P.O. Box 1180, 15462 Dasman, Kuwait
2
Faculty of Medicine, University of Helsinki, Helsinki, Finland
3
King Hussein Cancer Center, Amman, Jordan
4
Sidra Medical and Research Center, Doha, Qatar
5
Department of Public Health, University of Helsinki, Helsinki, Finland
6
Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland
7
McGill University and Genome Que
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