Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
Gaurav Thareja, Yasser Al‐Sarraj, Aziz Belkadi, Maryam Al-Motawa, Qatar Genome Project Management, Said I. Ismail, Wadha Al‐Muftah, Radja Badji, Hamdi Mbarek, Dima Darwish, Tasnim Fadl, Heba Yasin, Maryem Ennaifar, Rania G. Abdel‐latif, Fatima Alkuwari, Muhammad Arshad Alvi, Yasser Al‐Sarraj, Chadi Saad, Asmaa Althani, Biobank and Sample Preparation, Eleni Fethnou, Fatima Qafoud, Eiman Alkhayat, Nahla Afifi, Sequencing and Genotyping group, Sara Tomei, Wei Liu, Stephan Lorenz, Applied Bioinformatics Core, Najeeb Syed, Hakeem Almabrazi, Fazulur Rehaman Vempalli, Ramzi Temanni, Data Management and Computing Infrastructure group, Tariq Abu Saqri, Mohammedhusen Khatib, Mehshad Hamza, Tariq Abu Zaid, Ahmed El Khouly, Tushar Pathare, Shafeeq Poolat, Rashid Al‐Ali, Omar Albagha, Souhaila Al Khodor, Mashael Al‐Shafai, Ramin Badii, Lotfi Chouchane, Xavier Estivill, Khalid A. Fakhro, Younes Mokrab, Puthen V. Jithesh, Zohreh Tatari-Calderone, Karsten Suhre, Omar Albagha
Abstract
Clinical laboratory tests play a pivotal role in medical decision making, but little is known about their genetic variability between populations. We report a genome-wide association study with 45 clinically relevant traits from the population of Qatar using a whole genome sequencing approach in a discovery set of 6218 individuals and replication in 7768 subjects. Trait heritability is more similar between Qatari and European populations (r = 0.81) than with Africans (r = 0.44). We identify 281 distinct variant-trait-associations at genome wide significance that replicate known associations. Allele frequencies for replicated loci show higher correlations with European (r = 0.94) than with African (r = 0.85) or Japanese (r = 0.80) populations. We find differences in linkage disequilibrium patterns and in effect sizes of the replicated loci compared to previous reports. We also report 17 novel and Qatari-predominate signals providing insights into the biological pathways regulating these traits. We observe that European-derived polygenic scores (PGS) have reduced predictive performance in the Qatari population which could have implications for the translation of PGS between populations and their future application in precision medicine.