Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-12-18
pubmed:abstractText
ABSTRACT : Population structure occurs when a sample is composed of individuals with different ancestries and can result in excess type I error in genome-wide association studies. Genome-wide principal-component analysis (PCA) has become a popular method for identifying and adjusting for subtle population structure in association studies. Using the Genetic Analysis Workshop 16 (GAW16) NARAC data, we explore two unresolved issues concerning the use of genome-wide PCA to account for population structure in genetic associations studies: the choice of single-nucleotide polymorphism (SNP) subset and the choice of adjustment model. We computed PCs for subsets of genome-wide SNPs with varying levels of LD. The first two PCs were similar for all subsets and the first three PCs were associated with case status for all subsets. When the PCs associated with case status were included as covariates in an association model, the reduction in genomic inflation factor was similar for all SNP sets. Several models have been proposed to account for structure using PCs, but it is not yet clear whether the different methods will result in substantively different results for association studies with individuals of European descent. We compared genome-wide association p-values and results for two positive-control SNPs previously associated with rheumatoid arthritis using four PC adjustment methods as well as no adjustment and genomic control. We found that in this sample, adjusting for the continuous PCs or adjusting for discrete clusters identified using the PCs adequately accounts for the case-control population structure, but that a recently proposed randomization test performs poorly.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-10835412, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-11315092, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-14749714, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-15052271, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-15208781, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-16041375, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-16175503, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-16862161, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-17194218, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-17701901, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-17804836, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-17924333, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-17982456, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-18161052, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-18208327, http://linkedlifedata.com/resource/pubmed/commentcorrection/20017972-18596976
pubmed:language
eng
pubmed:journal
pubmed:status
PubMed-not-MEDLINE
pubmed:issn
1753-6561
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
3 Suppl 7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S108
pubmed:year
2009
pubmed:articleTitle
Principal-component-based population structure adjustment in the North American Rheumatoid Arthritis Consortium data: impact of single-nucleotide polymorphism set and analysis method.
pubmed:affiliation
Department of Biostatistics, Boston University School of Public Heath, Crosstown Center, 801 Massachusetts Avenue, 3rd Floor, Boston, Massachusetts 02118 USA. gpeloso@bu.edu.
pubmed:publicationType
Journal Article