In case-control association studies, population subdivision or admixture can lead to spurious associations between a phenotype and unlinked candidate loci. Population stratification can occur in case-control association studies when allele frequencies differ between cases and controls because of ancestry. We evaluated five methods (Fst, Genomic Control, STRUCTURE, PLINK and EIGENSTRAT) using 317K SNPs (Illumina HumanHap300) in a case-control sample of 200 American subjects with different races (Caucasian, African and Asian) in order to identify and to correct for stratification. Fst, Structure and Genomic Control are based on the usage of few genetic markers while PLINK and EIGENSTRAT are computationally tractable on a genome-wide scale. Fst, STRUCTURE and Genomic Control did not detect a significant stratification in our sample, as well as EIGENSTRAT and PLINK. However, these last two methods, using a much larger information from the whole set of SNPs, graphically suggested the presence of a partial stratification, due to African and Asian individuals while the estimated inflation factor of 1 didn't statistically confirm stratification. This brought to the decision to further enlarge the sample with hundreds of controls coming from Caucasian populations. When we enlarged the sample to 650 individuals we found a high value of inflation factor as statistical confirmation of the population stratification. The substructure still depends only on African and Asian subjects that are separated from the Caucasian homogeneous sample. Therefore the sample size is crucial to get enough power to detect a possible stratification.
|Titolo:||Comparison of different methods to estimate genetic ancestry and control for stratification in genome-wide association studies|
|Data di pubblicazione:||3-giu-2008|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
Settore MED/03 - Genetica Medica
|Enti collegati al convegno:||European Society of Human Genetics (ESHG)|
|Citazione:||Comparison of different methods to estimate genetic ancestry and control for stratification in genome-wide association studies / E. Salvi, G. Guffanti, A. Orro, F. Torri, S. Lupoli, J. Turner, D. Keator, J. Fallon, S. Potkin, C. Barlassina, D. Cusi, L. Milanesi, F. Macciardi. ((Intervento presentato al convegno European Human Genetics Conference tenutosi a Barcelona nel 2008.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|