Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies

Hua Tang; Tom Quertermous; Beatriz Rodriguez; Sharon L.R. Kardia; Xiaofeng Zhu; Andrew Brown; James S. Pankow; Michael A. Province; Steven C. Hunt; Eric Boerwinkle; Nicholas J. Schork; Neil J. Risch

doi:10.1086/427888

Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies

Hua Tang, Tom Quertermous, Beatriz Rodriguez, Sharon L.R. Kardia, Xiaofeng Zhu, Andrew Brown, James S. Pankow, Michael A. Province, Steven C. Hunt, Eric Boerwinkle, Nicholas J. Schork, Neil J. Risch

Epidemiology

Research output: Contribution to journal › Article › peer-review

440 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	268-275
Number of pages	8
Journal	American Journal of Human Genetics
Volume	76
Issue number	2
DOIs	https://doi.org/10.1086/427888
State	Published - Feb 2005

Bibliographical note

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).

Access

10.1086/427888

OpenUrl availability

Full text

Cite this

@article{f18fc55ea2de48bbaa6088398f6a3599,

title = "Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies",

abstract = "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.",

author = "Hua Tang and Tom Quertermous and Beatriz Rodriguez and Kardia, {Sharon L.R.} and Xiaofeng Zhu and Andrew Brown and Pankow, {James S.} and Province, {Michael A.} and Hunt, {Steven C.} and Eric Boerwinkle and Schork, {Nicholas J.} and Risch, {Neil J.}",

note = "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). ",

year = "2005",

month = feb,

doi = "10.1086/427888",

language = "English (US)",

volume = "76",

pages = "268--275",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "2",

}

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

UR - http://www.scopus.com/inward/citedby.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 -

Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies

Abstract

Bibliographical note

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this