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

<p dir="ltr">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 geno...

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Main Author: Gaurav Thareja (459188) (author)
Other Authors: The Qatar Genome Program Research (QGPR) Consortium (14157276) (author), Yasser Al-Sarraj (11721425) (author), Aziz Belkadi (779313) (author), Maryam Almotawa (14157279) (author), Karsten Suhre (67967) (author), Omar M. E. Albagha (11704871) (author)
Published: 2021
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author Gaurav Thareja (459188)
author2 The Qatar Genome Program Research (QGPR) Consortium (14157276)
Yasser Al-Sarraj (11721425)
Aziz Belkadi (779313)
Maryam Almotawa (14157279)
Karsten Suhre (67967)
Omar M. E. Albagha (11704871)
author2_role author
author
author
author
author
author
author_facet Gaurav Thareja (459188)
The Qatar Genome Program Research (QGPR) Consortium (14157276)
Yasser Al-Sarraj (11721425)
Aziz Belkadi (779313)
Maryam Almotawa (14157279)
Karsten Suhre (67967)
Omar M. E. Albagha (11704871)
author_role author
dc.creator.none.fl_str_mv Gaurav Thareja (459188)
The Qatar Genome Program Research (QGPR) Consortium (14157276)
Yasser Al-Sarraj (11721425)
Aziz Belkadi (779313)
Maryam Almotawa (14157279)
Karsten Suhre (67967)
Omar M. E. Albagha (11704871)
dc.date.none.fl_str_mv 2021-02-23T09:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41467-021-21381-3
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Whole_genome_sequencing_in_the_Middle_Eastern_Qatari_population_identifies_genetic_associations_with_45_clinically_relevant_traits/21601788
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
General Physics and Astronomy
General Biochemistry, Genetics and Molecular Biology
General Chemistry
dc.title.none.fl_str_mv Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1038/s41467-021-21381-3" target="_blank">http://dx.doi.org/10.1038/s41467-021-21381-3</a></p><p dir="ltr">Additional institutions affiliated with: The Qatar Genome Program Research (QGPR) Consortium</p>
eu_rights_str_mv openAccess
id Manara2_380d66974a59178c1a36691dca19819e
identifier_str_mv 10.1038/s41467-021-21381-3
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/21601788
publishDate 2021
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rights_invalid_str_mv CC BY 4.0
spelling Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traitsGaurav Thareja (459188)The Qatar Genome Program Research (QGPR) Consortium (14157276)Yasser Al-Sarraj (11721425)Aziz Belkadi (779313)Maryam Almotawa (14157279)Karsten Suhre (67967)Omar M. E. Albagha (11704871)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesClinical sciencesGeneral Physics and AstronomyGeneral Biochemistry, Genetics and Molecular BiologyGeneral Chemistry<p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1038/s41467-021-21381-3" target="_blank">http://dx.doi.org/10.1038/s41467-021-21381-3</a></p><p dir="ltr">Additional institutions affiliated with: The Qatar Genome Program Research (QGPR) Consortium</p>2021-02-23T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41467-021-21381-3https://figshare.com/articles/journal_contribution/Whole_genome_sequencing_in_the_Middle_Eastern_Qatari_population_identifies_genetic_associations_with_45_clinically_relevant_traits/21601788CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/216017882021-02-23T09:00:00Z
spellingShingle Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
Gaurav Thareja (459188)
Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
General Physics and Astronomy
General Biochemistry, Genetics and Molecular Biology
General Chemistry
status_str publishedVersion
title Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
title_full Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
title_fullStr Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
title_full_unstemmed Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
title_short Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
title_sort Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits
topic Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
General Physics and Astronomy
General Biochemistry, Genetics and Molecular Biology
General Chemistry