Genetic Structure of the Han Chinese Population Revealed by Genome-wide SNP Variation

Population stratification is a potential problem for genome-wide association studies (GWAS), confounding results and causing spurious associations. Hence, understanding how allele frequencies vary across geographic regions or among subpopulations is an important prelude to analyzing GWAS data. Using...

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Published in:American journal of human genetics 2009-12, Vol.85 (6), p.775-785
Main Authors: Chen, Jieming, Zheng, Houfeng, Bei, Jin-Xin, Sun, Liangdan, Jia, Wei-hua, Li, Tao, Zhang, Furen, Seielstad, Mark, Zeng, Yi-Xin, Zhang, Xuejun, Liu, Jianjun
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Language:English
Subjects:
Algorithms
Asian Continental Ancestry Group
Biological and medical sciences
China
Computer Simulation
Ethnic Groups
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genetic Variation - genetics
Genetics of eukaryotes. Biological and molecular evolution
Genetics, Population
Genome
Genome-Wide Association Study
Genomics
Humans
Medical genetics
Medical sciences
Migration
Minority & ethnic groups
Models, Genetic
Molecular and cellular biology
Polymorphism, Single Nucleotide
Population genetics
Simulation
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creator Chen, Jieming
Zheng, Houfeng
Bei, Jin-Xin
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Jia, Wei-hua
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Zhang, Furen
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Zeng, Yi-Xin
Zhang, Xuejun
Liu, Jianjun
description Population stratification is a potential problem for genome-wide association studies (GWAS), confounding results and causing spurious associations. Hence, understanding how allele frequencies vary across geographic regions or among subpopulations is an important prelude to analyzing GWAS data. Using over 350,000 genome-wide autosomal SNPs in over 6000 Han Chinese samples from ten provinces of China, our study revealed a one-dimensional “north-south” population structure and a close correlation between geography and the genetic structure of the Han Chinese. The north-south population structure is consistent with the historical migration pattern of the Han Chinese population. Metropolitan cities in China were, however, more diffused “outliers,” probably because of the impact of modern migration of peoples. At a very local scale within the Guangdong province, we observed evidence of population structure among dialect groups, probably on account of endogamy within these dialects. Via simulation, we show that empirical levels of population structure observed across modern China can cause spurious associations in GWAS if not properly handled. In the Han Chinese, geographic matching is a good proxy for genetic matching, particularly in validation and candidate-gene studies in which population stratification cannot be directly accessed and accounted for because of the lack of genome-wide data, with the exception of the metropolitan cities, where geographical location is no longer a good indicator of ancestral origin. Our findings are important for designing GWAS in the Chinese population, an activity that is expected to intensify greatly in the near future.
doi_str_mv 10.1016/j.ajhg.2009.10.016
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subjects Algorithms
Asian Continental Ancestry Group
Biological and medical sciences
China
Computer Simulation
Ethnic Groups
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genetic Variation - genetics
Genetics of eukaryotes. Biological and molecular evolution
Genetics, Population
Genome
Genome-Wide Association Study
Genomics
Humans
Medical genetics
Medical sciences
Migration
Minority & ethnic groups
Models, Genetic
Molecular and cellular biology
Polymorphism, Single Nucleotide
Population genetics
Simulation
title Genetic Structure of the Han Chinese Population Revealed by Genome-wide SNP Variation
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