Genome-wide landscape establishes novel association signals for metabolic traits in the Arab population

• DOI: 10.1007/s00439-020-02222-7
• Publication Date: 2020-09-10T11:42:31Z
• Authors: Prashantha Hebbar; Jehad Ahmed Abubaker; Mohamed Abu-Farha; Osama Alsmadi; Naser Elkum; Fadi Alkayal; Sumi Elsa John; Arshad Channanath; Rasheeba Iqbal; Janne Pitkaniemi; Jaakko Tuomilehto; Robert Sladek; Fahd Al-Mulla; Thangavel Alphons...
• Keywords: Genome-wide Association Study; Genetic Association; 1000 Genomes Project; Human genetics

Abstract While the Arabian population has a high prevalence of metabolic disorders, it not been included in global studies that identify genetic risk loci for traits. Determining transferability such largely Euro-centric established is essential to transfer research tools/resources, and drug targets generated by broad range ethnic populations. Further, consideration populations as Arabs, are characterized consanguinity level inbreeding, can lead identification novel loci. We imputed published GWAS data from two Kuwaiti Arab cohorts ( n = 1434 1298) 1000 Genomes Project haplotypes performed meta-analysis associations with 13 compared observed association signals those Our study highlighted 70 variants 9 different genes, some which have links disorders. By relaxing genome-wide significance threshold, we identified ‘novel’ 11 genes Many variant were at or borderline significance. Furthermore, 349 previously 187 validated our study. Pleiotropic effect on multiple traits observed. Fine-mapping illuminated rs7838666/ CSMD1 rs1864163/ CETP rs112861901/[ INTS10,LPL ] candidate causal influencing fasting plasma glucose high-density lipoprotein levels. Computational functional analysis variety gene regulatory around several variants. This enlarges ancestry diversity available elucidates new an group burdened