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    Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits

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    Date
    2021-02-23
    Author
    Thareja, Gaurav
    Al-Sarraj, Yasser
    Belkadi, Aziz
    Almotawa, Maryam
    Ismail, Said
    Al-Muftah, Wadha
    Badji, Radja
    Mbarek, Hamdi
    Darwish, Dima
    Fadl, Tasnim
    Yasin, Heba
    Ennaifar, Maryem
    Abdellatif, Rania
    Alkuwari, Fatima
    Alvi, Muhammad
    Saad, Chadi
    Althani, Asmaa
    Fethnou, Eleni
    Qafoud, Fatima
    Alkhayat, Eiman
    Afifi, Nahla
    Tomei, Sara
    Liu, Wei
    Lorenz, Stephan
    Syed, Najeeb
    Almabrazi, Hakeem
    Vempalli, Fazulur Rehaman
    Temanni, Ramzi
    Saqri, Tariq Abu
    Khatib, Mohammedhusen
    Hamza, Mehshad
    Zaid, Tariq Abu
    El Khouly, Ahmed
    Pathare, Tushar
    Poolat, Shafeeq
    Al-Ali, Rashid
    Albagha, Omar M.E.
    Al-Khodor, Souhaila
    Alshafai, Mashael
    Badii, Ramin
    Chouchane, Lotfi
    Estivill, Xavier
    Fakhro, Khalid
    Mokrab, Younes
    Puthen, Jithesh
    Tatari, Zohreh
    Suhre, Karsten
    ...show more authors ...show less authors
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    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.
    URI
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85101943095&origin=inward
    DOI/handle
    http://dx.doi.org/10.1038/s41467-021-21381-3
    http://hdl.handle.net/10576/58912
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    • QU Health Research [‎110‎ items ]

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