Genetic analyses identify widespread sex-differential participation bias

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 e...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Nature genetics Ročník 53; číslo 5; s. 663 - 671
Hlavní autori:	Pirastu, Nicola, Cordioli, Mattia, Nandakumar, Priyanka, Mignogna, Gianmarco, Abdellaoui, Abdel, Hollis, Benjamin, Kanai, Masahiro, Rajagopal, Veera M., Parolo, Pietro Della Briotta, Baya, Nikolas, Carey, Caitlin E., Karjalainen, Juha, Als, Thomas D., Van der Zee, Matthijs D., Day, Felix R., Ong, Ken K., Morisaki, Takayuki, de Geus, Eco, Bellocco, Rino, Okada, Yukinori, Børglum, Anders D., Joshi, Peter, Auton, Adam, Hinds, David, Neale, Benjamin M., Walters, Raymond K., Nivard, Michel G., Perry, John R. B., Ganna, Andrea
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.05.2021 Nature Publishing Group
Predmet:	45 45/43 631/208 631/208/1515 631/208/205 631/208/205/2138 Adult Agriculture Animal Genetics and Genomics Bias Biobanks Biological Specimen Banks Biomedical and Life Sciences Biomedicine Body mass index Body size Cancer Research Chromosomes, Human - genetics Demographic aspects Female Females Gene Function Genetic analysis Genetic aspects Genetic Loci Genetic research Genome-wide association studies Genome-Wide Association Study Genomes Genotype & phenotype Genotypes Heritability Human Genetics Humans Influence Inheritance Patterns - genetics Male Males Mortality Participation Polymorphism, Single Nucleotide - genetics Psychological aspects Quality control Sample Size Set (Psychology) Sex Sex Characteristics Sex chromosomes Sex differences (Psychology) Sexes Subgroups United Kingdom United Kingdom United Kingdom > UK Japan
ISSN:	1061-4036, 1546-1718, 1546-1718
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	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. Genetic analyses identify widespread sex-differential participation bias in population-based studies and show how this bias can lead to incorrect inferences. These findings highlight new challenges for association studies as sample sizes continue to grow.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work.
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/s41588-021-00846-7