Polygenic risk score for schizophrenia is more strongly associated with ancestry than with schizophrenia.

Psychiatric Genetics
David Curtis

Abstract

The polygenic risk score (PRS) for schizophrenia, derived from very large numbers of weakly associated genetic markers, has been repeatedly shown to be robustly associated with schizophrenia in independent samples and also with other diseases and traits. This study aims to explore the distribution of the schizophrenia PRS in subjects of different ancestry. The schizophrenia PRS derived from the large genome-wide association study carried out by the Psychiatric Genetics Consortium was calculated using the downloaded genotypes of HapMap subjects from 11 different ancestral groups. It was also calculated using downloaded genotypes of European schizophrenia cases and controls from the CommonMind Consortium. The PRS for schizophrenia varied significantly between ancestral groups (P<2×10(-16)) and was much higher in African than European HapMap subjects. The mean difference between these groups was 10 times as high as the mean difference between European schizophrenia cases and controls. The distributions of scores for African and European subjects hardly overlapped. The PRS cannot be regarded as simply a measure of the polygenic contribution to risk of schizophrenia and clearly contains a strong ancestry component. It is possible th...Continue Reading

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Citations

Oct 29, 2018·Genetic Epidemiology·Kelsey E GrindeTamar Sofer
Jan 20, 2019·Genetic Epidemiology·Inke R König
Aug 1, 2019·Human Molecular Genetics·Samuel A LambertMichael Inouye
Oct 22, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Amanda K TilotSimon E Fisher
Apr 7, 2020·Journal of Genetic Counseling·Saghira M SharifMaggie Kirk
Jan 10, 2020·The Journal of Clinical Endocrinology and Metabolism·Yoonjung Yoonie JooUNKNOWN International PCOS Consortium
Mar 31, 2019·Nature Genetics·Alicia R MartinMark J Daly
Aug 27, 2019·F1000Research·Janice M Fullerton, John I Nurnberger
Jan 20, 2019·Nature Communications·Simon HaworthNicholas J Timpson
Feb 1, 2020·Science·S GulsunerJ M McClellan
Apr 30, 2019·Royal Society Open Science·Rebecca B LawnMarcus R Munafò
Aug 1, 2019·Human Molecular Genetics·Guhan R Venkataraman, Manuel A Rivas
Sep 4, 2020·G3 : Genes - Genomes - Genetics·Bárbara D Bitarello, Iain Mathieson
Feb 9, 2021·Psychological Medicine·Sophie E LeggeKaarina Kowalec
Feb 12, 2021·Nature·Ambroise Wonkam
Mar 18, 2021·International Journal of Epidemiology·Kenneth EkoruCharles N Rotimi
Aug 28, 2021·Journal of Personalized Medicine·Bartha M KnoppersNora Pashayan
Sep 17, 2021·PLoS Genetics·Lars G FritscheBhramar Mukherjee

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Methods Mentioned

BETA
genotyping
RNAseq
chip
pull down

Software Mentioned

plink
R

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