TY - JOUR
T1 - Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies
AU - Tang, Hua
AU - Quertermous, Tom
AU - Rodriguez, Beatriz
AU - Kardia, Sharon L.R.
AU - Zhu, Xiaofeng
AU - Brown, Andrew
AU - Pankow, James S.
AU - Province, Michael A.
AU - Hunt, Steven C.
AU - Boerwinkle, Eric
AU - Schork, Nicholas J.
AU - Risch, Neil J.
N1 - Funding Information:
The FBPP is a collaborative effort of four research networks (GenNet, GENOA, HyperGEN, and SAPPHIRe) that aims to investigate high blood pressure and related conditions in multiple racial/ethnic groups (FBPP Investigators 2002 ). Each network has been funded by the National Heart, Lung, and Blood Institute (NHLBI) since 1995. In total, DNA samples from 10,527 participants were genotyped at 326 autosomal genome screen microsatellite markers by the NHLBI-sponsored Mammalian Genotyping Service (Marshfield, WI) (screening set 8) and had sufficient marker data for analysis (i.e., at most 40 missing genotypes).
PY - 2005/2
Y1 - 2005/2
N2 - We have analyzed genetic data for 326 microsatellite markers that were typed uniformly in a large multiethnic population-based sample of individuals as part of a study of the genetics of hypertension (Family Blood Pressure Program). Subjects identified themselves as belonging to one of four major racial/ethnic groups (white, African American, East Asian, and Hispanic) and were recruited from 15 different geographic locales within the United States and Taiwan. Genetic cluster analysis of the microsatellite markers produced four major clusters, which showed near-perfect correspondence with the four self-reported race/ethnicity categories. Of 3,636 subjects of varying race/ethnicity, only 5 (0.14%) showed genetic cluster membership different from their self-identified race/ethnicity. On the other hand, we detected only modest genetic differentiation between different current geographic locales within each race/ethnicity group. Thus, ancient geographic ancestry, which is highly correlated with self-identified race/ethnicity-as opposed to current residence-is the major determinant of genetic structure in the U.S. population. Implications of this genetic structure for case-control association studies are discussed.
AB - We have analyzed genetic data for 326 microsatellite markers that were typed uniformly in a large multiethnic population-based sample of individuals as part of a study of the genetics of hypertension (Family Blood Pressure Program). Subjects identified themselves as belonging to one of four major racial/ethnic groups (white, African American, East Asian, and Hispanic) and were recruited from 15 different geographic locales within the United States and Taiwan. Genetic cluster analysis of the microsatellite markers produced four major clusters, which showed near-perfect correspondence with the four self-reported race/ethnicity categories. Of 3,636 subjects of varying race/ethnicity, only 5 (0.14%) showed genetic cluster membership different from their self-identified race/ethnicity. On the other hand, we detected only modest genetic differentiation between different current geographic locales within each race/ethnicity group. Thus, ancient geographic ancestry, which is highly correlated with self-identified race/ethnicity-as opposed to current residence-is the major determinant of genetic structure in the U.S. population. Implications of this genetic structure for case-control association studies are discussed.
UR - http://www.scopus.com/inward/record.url?scp=19944432946&partnerID=8YFLogxK
U2 - 10.1086/427888
DO - 10.1086/427888
M3 - Article
C2 - 15625622
AN - SCOPUS:19944432946
SN - 0002-9297
VL - 76
SP - 268
EP - 275
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -