Accounting for ancestry

Population substructure and genome-wide association studies

Chao Tian, Peter K. Gregersen, Michael F Seldin

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

Accounting for the genetic substructure of human populations has become a major practical issue for studying complex genetic disorders. Allele frequency differences among ethnic groups and subgroups and admixture between different ethnic groups can result in frequent false-positive results or reduced power in genetic studies. Here, we review the problems and progress in defining population differences and the application of statistical methods to improve association studies. It is now possible to take into account the confounding effects of population stratification using thousands of unselected genome-wide single-nucleotide polymorphisms or, alternatively, selected panels of ancestry informative markers. These methods do not require any demographic information and therefore can be widely applied to genotypes available from multiple sources. We further suggest that it will be important to explore results in homogeneous population subsets as we seek to define the extent to which genomic variation influences complex phenotypes.

Original languageEnglish (US)
JournalHuman Molecular Genetics
Volume17
Issue numberR2
DOIs
StatePublished - Oct 15 2008

Fingerprint

Genome-Wide Association Study
Ethnic Groups
Population
Inborn Genetic Diseases
Medical Genetics
Gene Frequency
Single Nucleotide Polymorphism
Genotype
Demography
Genome
Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Accounting for ancestry : Population substructure and genome-wide association studies. / Tian, Chao; Gregersen, Peter K.; Seldin, Michael F.

In: Human Molecular Genetics, Vol. 17, No. R2, 15.10.2008.

Research output: Contribution to journalArticle

@article{265414b6796c4d7db5ccd34038d3b0de,
title = "Accounting for ancestry: Population substructure and genome-wide association studies",
abstract = "Accounting for the genetic substructure of human populations has become a major practical issue for studying complex genetic disorders. Allele frequency differences among ethnic groups and subgroups and admixture between different ethnic groups can result in frequent false-positive results or reduced power in genetic studies. Here, we review the problems and progress in defining population differences and the application of statistical methods to improve association studies. It is now possible to take into account the confounding effects of population stratification using thousands of unselected genome-wide single-nucleotide polymorphisms or, alternatively, selected panels of ancestry informative markers. These methods do not require any demographic information and therefore can be widely applied to genotypes available from multiple sources. We further suggest that it will be important to explore results in homogeneous population subsets as we seek to define the extent to which genomic variation influences complex phenotypes.",
author = "Chao Tian and Gregersen, {Peter K.} and Seldin, {Michael F}",
year = "2008",
month = "10",
day = "15",
doi = "10.1093/hmg/ddn268",
language = "English (US)",
volume = "17",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "R2",

}

TY - JOUR

T1 - Accounting for ancestry

T2 - Population substructure and genome-wide association studies

AU - Tian, Chao

AU - Gregersen, Peter K.

AU - Seldin, Michael F

PY - 2008/10/15

Y1 - 2008/10/15

N2 - Accounting for the genetic substructure of human populations has become a major practical issue for studying complex genetic disorders. Allele frequency differences among ethnic groups and subgroups and admixture between different ethnic groups can result in frequent false-positive results or reduced power in genetic studies. Here, we review the problems and progress in defining population differences and the application of statistical methods to improve association studies. It is now possible to take into account the confounding effects of population stratification using thousands of unselected genome-wide single-nucleotide polymorphisms or, alternatively, selected panels of ancestry informative markers. These methods do not require any demographic information and therefore can be widely applied to genotypes available from multiple sources. We further suggest that it will be important to explore results in homogeneous population subsets as we seek to define the extent to which genomic variation influences complex phenotypes.

AB - Accounting for the genetic substructure of human populations has become a major practical issue for studying complex genetic disorders. Allele frequency differences among ethnic groups and subgroups and admixture between different ethnic groups can result in frequent false-positive results or reduced power in genetic studies. Here, we review the problems and progress in defining population differences and the application of statistical methods to improve association studies. It is now possible to take into account the confounding effects of population stratification using thousands of unselected genome-wide single-nucleotide polymorphisms or, alternatively, selected panels of ancestry informative markers. These methods do not require any demographic information and therefore can be widely applied to genotypes available from multiple sources. We further suggest that it will be important to explore results in homogeneous population subsets as we seek to define the extent to which genomic variation influences complex phenotypes.

UR - http://www.scopus.com/inward/record.url?scp=57549090341&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57549090341&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddn268

DO - 10.1093/hmg/ddn268

M3 - Article

VL - 17

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - R2

ER -