Assessing the impact of population stratification on genetic association studies

Autor:	Stacey Gabriel, Laurence N. Kolonel, Matthew L. Freedman, David Altshuler, Michele T. Pato, Eric J. Topol, Andre A. Mignault, Pamela Sklar, Carlos N. Pato, Gavin J. McDonald, Brian E. Henderson, Nick Patterson, Tracey L. Petryshen, Joel N. Hirschhorn, Jordan W. Smoller, David Reich, Eric S. Lander, Kathryn L. Penney
Rok vydání:	2004
Předmět:	Genetics Mutation Missense Population genetics Disease Biology Population stratification Polymorphism Single Nucleotide Stratification (mathematics) Cohort Studies Genetics Population Genetic marker Case-Control Studies Humans Genotyping Allele frequency Genetic association Demography
Zdroj:	Nature Genetics. 36:388-393
ISSN:	1546-1718 1061-4036
DOI:	10.1038/ng1333
Popis:	Population stratification refers to differences in allele frequencies between cases and controls due to systematic differences in ancestry rather than association of genes with disease. It has been proposed that false positive associations due to stratification can be controlled by genotyping a few dozen unlinked genetic markers. To assess stratification empirically, we analyzed data from 11 case-control and case-cohort association studies. We did not detect statistically significant evidence for stratification but did observe that assessments based on a few dozen markers lack power to rule out moderate levels of stratification that could cause false positive associations in studies designed to detect modest genetic risk factors. After increasing the number of markers and samples in a case-cohort study (the design most immune to stratification), we found that stratification was in fact present. Our results suggest that modest amounts of stratification can exist even in well designed studies.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd19c36f98df4a617e2b25fdfedd99cf https://doi.org/10.1038/ng1333 Zobrazit plný text záznamu Plný text ve formátu PDF