NDLI: ROADTRIPS: Case-Control Association Testing with Partially or Completely Unknown Population and Pedigree Structure

Content Provider	PubMed Central
Author	Thornton, Timothy Mcpeek, Mary Sara
Copyright Year	2010
Abstract	Genome-wide association studies are routinely conducted to identify genetic variants that influence complex disorders. It is well known that failure to properly account for population or pedigree structure can lead to spurious association as well as reduced power. We propose a method, ROADTRIPS, for case-control association testing in samples with partially or completely unknown population and pedigree structure. ROADTRIPS uses a covariance matrix estimated from genome-screen data to correct for unknown population and pedigree structure while maintaining high power by taking advantage of known pedigree information when it is available. ROADTRIPS can incorporate data on arbitrary combinations of related and unrelated individuals and is computationally feasible for the analysis of genetic studies with millions of markers. In simulations with related individuals and population structure, including admixture, we demonstrate that ROADTRIPS provides a substantial improvement over existing methods in terms of power and type 1 error. The ROADTRIPS method can be used across a variety of study designs, ranging from studies that have a combination of unrelated individuals and small pedigrees to studies of isolated founder populations with partially known or completely unknown pedigrees. We apply the method to analyze two data sets: a study of rheumatoid arthritis in small UK pedigrees, from Genetic Analysis Workshop 15, and data from the Collaborative Study of the Genetics of Alcoholism on alcohol dependence in a sample of moderate-size pedigrees of European descent, from Genetic Analysis Workshop 14. We detect genome-wide significant association, after Bonferroni correction, in both studies.
Related Links	http://dx.doi.org/10.1016/j.ajhg.2010.01.001
Ending Page	184
Page Count	13
Starting Page	172
File Format	PDF
ISSN	00029297
e-ISSN	15376605
Journal	American Journal of Human Genetics
Issue Number	2
Volume Number	86
Language	English
Publisher	Elsevier
Publisher Date	2010-02-01
Access Restriction	Open
Rights Holder	Elsevier
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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