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

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 d...

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Bibliographic Details
Published in:Nature communications Vol. 12; no. 1; pp. 1250 - 10
Main Authors: Thareja, Gaurav, Al-Sarraj, Yasser, Belkadi, Aziz, Almotawa, Maryam, Suhre, Karsten, Albagha, Omar M. E.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 23.02.2021
Nature Publishing Group
Nature Portfolio
Subjects:
45/23
45/43
45/61
45/71
45/91
631/208/205/2138
692/308/2056
Biological Specimen Banks
Decision making
Gene frequency
Gene Frequency - genetics
Gene sequencing
Genetic Loci
Genetic variability
Genetics, Population
Genome, Human
Genome-wide association studies
Genome-Wide Association Study
Genomes
Heritability
Humanities and Social Sciences
Humans
Japan
Laboratory tests
Linkage disequilibrium
Linkage Disequilibrium - genetics
Loci
multidisciplinary
Multifactorial Inheritance - genetics
Performance prediction
Polygenic inheritance
Population genetics
Populations
Precision medicine
Principal Component Analysis
Qatar
Quantitative Trait, Heritable
Science
Science (multidisciplinary)
Sequence Analysis, DNA
Whole genome sequencing
Japan
Qatar
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. The genetic basis for traits can vary between populations. Here the authors report a genome wide association study with 45 clinically-relevant traits in individuals from Qatar, replicating many known loci and identifying new Qatari-predominant signals.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-21381-3