Effects of Cis and Trans Genetic Ancestry on Gene Expression in African Americans

Overview

Journal PLoS Genet

Specialty Genetics

Date 2008 Dec 6

PMID 19057673

Citations 59

Authors

Alkes L Price

Nick Patterson

Dustin C Hancks

Simon Myers

David Reich

Vivian G Cheung

Richard S Spielman

Affiliations

Soon will be listed here.

Abstract

Variation in gene expression is a fundamental aspect of human phenotypic variation. Several recent studies have analyzed gene expression levels in populations of different continental ancestry and reported population differences at a large number of genes. However, these differences could largely be due to non-genetic (e.g., environmental) effects. Here, we analyze gene expression levels in African American cell lines, which differ from previously analyzed cell lines in that individuals from this population inherit variable proportions of two continental ancestries. We first relate gene expression levels in individual African Americans to their genome-wide proportion of European ancestry. The results provide strong evidence of a genetic contribution to expression differences between European and African populations, validating previous findings. Second, we infer local ancestry (0, 1, or 2 European chromosomes) at each location in the genome and investigate the effects of ancestry proximal to the expressed gene (cis) versus ancestry elsewhere in the genome (trans). Both effects are highly significant, and we estimate that 12+/-3% of all heritable variation in human gene expression is due to cis variants.

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References

Emilsson V, Thorleifsson G, Zhang B, Leonardson A, Zink F, Zhu J . Genetics of gene expression and its effect on disease. Nature. 2008; 452(7186):423-8. DOI: 10.1038/nature06758. View

Holmes E, Loo R, Stamler J, Bictash M, Yap I, Chan Q . Human metabolic phenotype diversity and its association with diet and blood pressure. Nature. 2008; 453(7193):396-400. PMC: 6556779. DOI: 10.1038/nature06882. View

Nalls M, Wilson J, Patterson N, Tandon A, Zmuda J, Huntsman S . Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies. Am J Hum Genet. 2008; 82(1):81-7. PMC: 2253985. DOI: 10.1016/j.ajhg.2007.09.003. View

Morley M, Molony C, Weber T, Devlin J, Ewens K, Spielman R . Genetic analysis of genome-wide variation in human gene expression. Nature. 2004; 430(7001):743-7. PMC: 2966974. DOI: 10.1038/nature02797. View

Spielman R, Bastone L, Burdick J, Morley M, Ewens W, Cheung V . Common genetic variants account for differences in gene expression among ethnic groups. Nat Genet. 2007; 39(2):226-31. PMC: 3005333. DOI: 10.1038/ng1955. View

Cheung V, Spielman R, Ewens K, Weber T, Morley M, Burdick J . Mapping determinants of human gene expression by regional and genome-wide association. Nature. 2005; 437(7063):1365-9. PMC: 3005311. DOI: 10.1038/nature04244. View

Stranger B, Nica A, Forrest M, Dimas A, Bird C, Beazley C . Population genomics of human gene expression. Nat Genet. 2007; 39(10):1217-24. PMC: 2683249. DOI: 10.1038/ng2142. View

Hughes K, Ayroles J, Reedy M, M Drnevich J, Rowe K, Ruedi E . Segregating variation in the transcriptome: cis regulation and additivity of effects. Genetics. 2006; 173(3):1347-55. PMC: 1526654. DOI: 10.1534/genetics.105.051474. View

Schadt E, Molony C, Chudin E, Hao K, Yang X, Lum P . Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008; 6(5):e107. PMC: 2365981. DOI: 10.1371/journal.pbio.0060107. View

10.

Wang H, Fu Y, McPeek M, Lu X, Nuzhdin S, Xu A . Complex genetic interactions underlying expression differences between Drosophila races: analysis of chromosome substitutions. Proc Natl Acad Sci U S A. 2008; 105(17):6362-7. PMC: 2359775. DOI: 10.1073/pnas.0711774105. View

11.

Storey J, Madeoy J, Strout J, Wurfel M, Ronald J, Akey J . Gene-expression variation within and among human populations. Am J Hum Genet. 2007; 80(3):502-9. PMC: 1821107. DOI: 10.1086/512017. View

12.

Akey J, Biswas S, Leek J, Storey J . On the design and analysis of gene expression studies in human populations. Nat Genet. 2007; 39(7):807-8. DOI: 10.1038/ng0707-807. View

13.

Parra E, Kittles R, Shriver M . Implications of correlations between skin color and genetic ancestry for biomedical research. Nat Genet. 2004; 36(11 Suppl):S54-60. DOI: 10.1038/ng1440. View

14.

Zhang W, Duan S, Kistner E, Bleibel W, Huang R, Clark T . Evaluation of genetic variation contributing to differences in gene expression between populations. Am J Hum Genet. 2008; 82(3):631-40. PMC: 2427223. DOI: 10.1016/j.ajhg.2007.12.015. View

15.

Fyr C, Kanaya A, Cummings S, Reich D, Hsueh W, Reiner A . Genetic admixture, adipocytokines, and adiposity in Black Americans: the Health, Aging, and Body Composition study. Hum Genet. 2007; 121(5):615-24. DOI: 10.1007/s00439-007-0353-z. View

16.

Gilad Y, Rifkin S, Pritchard J . Revealing the architecture of gene regulation: the promise of eQTL studies. Trends Genet. 2008; 24(8):408-15. PMC: 2583071. DOI: 10.1016/j.tig.2008.06.001. View

17.

Dixon A, Liang L, Moffatt M, Chen W, Heath S, Wong K . A genome-wide association study of global gene expression. Nat Genet. 2007; 39(10):1202-7. DOI: 10.1038/ng2109. View

18.

Patterson N, Price A, Reich D . Population structure and eigenanalysis. PLoS Genet. 2006; 2(12):e190. PMC: 1713260. DOI: 10.1371/journal.pgen.0020190. View

19.

Frazer K, Ballinger D, Cox D, Hinds D, Stuve L, Boudreau A . A second generation human haplotype map of over 3.1 million SNPs. Nature. 2007; 449(7164):851-61. PMC: 2689609. DOI: 10.1038/nature06258. View

20.

Goring H, Curran J, Johnson M, Dyer T, Charlesworth J, Cole S . Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nat Genet. 2007; 39(10):1208-16. DOI: 10.1038/ng2119. View