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Genetic analyses identify widespread sex-differential participation bias

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FinnGen Study. / Genetic analyses identify widespread sex-differential participation bias. I: Nature Genetics. 2021 ; Bind 53, Nr. 5. s. 663-671.

Bibtex

@article{865e7c0b411646b6a0111b10ea055218,
title = "Genetic analyses identify widespread sex-differential participation bias",
abstract = "Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index-increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10-36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.",
keywords = "Adult, Artifacts, Bias, Biological Specimen Banks, Chromosomes, Human/genetics, Female, Genetic Loci, Genome-Wide Association Study, Humans, Inheritance Patterns/genetics, Male, Polymorphism, Single Nucleotide/genetics, Sample Size, Sex Characteristics, United Kingdom",
author = "Nicola Pirastu and Mattia Cordioli and Priyanka Nandakumar and Gianmarco Mignogna and Abdel Abdellaoui and Benjamin Hollis and Masahiro Kanai and Rajagopal, {Veera M} and Parolo, {Pietro Della Briotta} and Nikolas Baya and Carey, {Caitlin E} and Juha Karjalainen and Als, {Thomas D} and {Van der Zee}, {Matthijs D} and Day, {Felix R} and Ong, {Ken K} and Takayuki Morisaki and {de Geus}, Eco and Rino Bellocco and Yukinori Okada and B{\o}rglum, {Anders D} and Peter Joshi and Adam Auton and David Hinds and Neale, {Benjamin M} and Walters, {Raymond K} and Nivard, {Michel G} and Perry, {John R B} and Andrea Ganna and {FinnGen Study}",
year = "2021",
month = may,
doi = "10.1038/s41588-021-00846-7",
language = "English",
volume = "53",
pages = "663--671",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "5",

}

RIS

TY - JOUR

T1 - Genetic analyses identify widespread sex-differential participation bias

AU - Pirastu, Nicola

AU - Cordioli, Mattia

AU - Nandakumar, Priyanka

AU - Mignogna, Gianmarco

AU - Abdellaoui, Abdel

AU - Hollis, Benjamin

AU - Kanai, Masahiro

AU - Rajagopal, Veera M

AU - Parolo, Pietro Della Briotta

AU - Baya, Nikolas

AU - Carey, Caitlin E

AU - Karjalainen, Juha

AU - Als, Thomas D

AU - Van der Zee, Matthijs D

AU - Day, Felix R

AU - Ong, Ken K

AU - Morisaki, Takayuki

AU - de Geus, Eco

AU - Bellocco, Rino

AU - Okada, Yukinori

AU - Børglum, Anders D

AU - Joshi, Peter

AU - Auton, Adam

AU - Hinds, David

AU - Neale, Benjamin M

AU - Walters, Raymond K

AU - Nivard, Michel G

AU - Perry, John R B

AU - Ganna, Andrea

AU - FinnGen Study

PY - 2021/5

Y1 - 2021/5

N2 - Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index-increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10-36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

AB - Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index-increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10-36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

KW - Adult

KW - Artifacts

KW - Bias

KW - Biological Specimen Banks

KW - Chromosomes, Human/genetics

KW - Female

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Humans

KW - Inheritance Patterns/genetics

KW - Male

KW - Polymorphism, Single Nucleotide/genetics

KW - Sample Size

KW - Sex Characteristics

KW - United Kingdom

UR - http://www.scopus.com/inward/record.url?scp=85105825849&partnerID=8YFLogxK

U2 - 10.1038/s41588-021-00846-7

DO - 10.1038/s41588-021-00846-7

M3 - Journal article

C2 - 33888908

VL - 53

SP - 663

EP - 671

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -

ID: 65786507