Fine-Scale Patterns of Population Stratification Confound Rare Variant Association Tests

PLoS ONE

Volumn 8, Issue 7, 2013, Pages

  O'Connor, Timothy D ^a   Kiezun, Adam ^b,c   Bamshad, Michael ^a,d   Rich, Stephen S ^e   Smith, Joshua D ^a   Turner, Emily ^a   Leal, Suzanne M ^f   Akey, Joshua M ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF VIRGINIA   (United States)

^f BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLELE; ARTICLE; EXOME; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; POPULATION DISTRIBUTION; POPULATION MOVEMENT PATTERN; POPULATION STRUCTURE; PRINCIPAL COMPONENT ANALYSIS; SIMULATION;

EID: 84879835789     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0065834     Document Type: Article

References (39)

1. Pritchard JK, Stephens M, Rosenberg NA, Donnelly P, (2000) Association mapping in structured populations. Am J Hum Genet 67: 170-181.
2. Ziv E, Burchard EG, (2003) Human population structure and genetic association studies. Pharmacogenomics 4: 431-441.
3. Clayton DG, Walker NM, Smyth DJ, Pask R, Cooper JD, et al. (2005) Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat Genet 37: 1243-1246.
4. Roeder K, Luca D, (2009) Searching for disease susceptibility variants in structured populations. Genomics 93: 1-4.
5. Helgason A, Yngvad'ottir B, Hrafnkelsson B, Gulcher J, Stef'ansson K, (2004) An Icelandic example of the impact of population structure on association studies. Nat Genet 37: 90-95.
6. The Wellcome Trust Case Control Consortium, (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661-678.
7. Roy-Gagnon MH, Moreau C, Bherer C, St-Onge P, Sinnett D, et al. (2011) Genomic and genealogical investigation of the French Canadian founder population structure. Hum Genet 129: 521-531.
8. Campbell CD, Ogburn EL, Lunetta KL, Lyon HN, Freedman ML, et al. (2005) Demonstrating stratification in a European American population. Nat Genet 37: 868-872.
9. Seldin MF, Shigeta R, Villoslada P, Selmi C, Tuomilehto J, et al. (2006) European population substructure: clustering of northern and southern populations. PLoS Genet 2: e143 doi:10.1371/journal.pgen.0020143.
10. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38: 904-909.
11. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747-753.
12. Eichler EE, Flint J, Gibson G, Kong A, Leal SM, et al. (2010) Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet 11: 446-450.
13. Bansal V, Libiger O, Torkamani A, Schork NJ, (2010) Statistical analysis strategies for association studies involving rare variants. Nat Rev Genet 11: 773-785.
14. Asimit J, Zeggini E, (2010) Rare variant association analysis methods for complex traits. Annu Rev Genet 44: 293-308.
15. Li B, Leal SM, (2008) Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet 83: 311-321.
16. Morris AP, Zeggini E, (2010) An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet Epidemiol 34: 188-193.
17. Tennessen JA, Bigham AW, O'Connor TD, Fu W, Kenny EE et al. (2012) Evolution and functional impact of rare coding variation from deep sequencing of 2,440 human exomes. Science DOI:10.1126/science.1219240.
18. Tintle N, Aschard H, Hu I, Nock N, Wang H, Pugh E. 2011. Inflated type I error rates when using aggregation methods to analyze rare variants in the 1000 Genomes Project exon sequencing data in unrelated individuals: summary results from Group 7 at Genetic Analysis Workshop 17. Genet Epidemiol 35: S56-S60.
19. The 1000 Genomes Project Consortium. 2010. A map of human genome variation from population-scale sequencing. Nature 467: 1061-1073.
20. Mathieson I, McVean G. 2012. Differential confounding of rare and common variants in spatially structured populations. Nat Genet 44: 243-246.
21. Kiezun A, Garimella K, Do R, Stitziel NO, Neale BM, et al. (2012) Exome sequencing and the genetic basis of complex traits. Nat Genet 44: 623-630.
22. Nelson MR, Wegmann D, Ehm MG, Kessner D, St. Jean P et al. (2012) An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People. Science DOI:10.1126/science.1217876.
23. Madsen BE, Browning SR, (2009) A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet 5: e1000384 doi:10.1371/journal.pgen.1000384.
24. Price AL, Kryukov GV, de Bakker PI, Purcell SM, Staples J, et al. (2010) Pooled Association Tests for Rare Variants in Exon-Resequencing Studies. Am J Hum Genet 86: 832-838.
25. Bhatia G, Bansal V, Harismendy O, Schork NJ, Topol EJ, et al. (2010) A covering method for detecting genetic associations between rare variants and common phenotypes. PLoS Comp Biol 6: e1000954 doi:10.1371/journal.pcbi.1000954.
26. Hoffmann TJ, Marini NJ, Witte JS, Lewin A, (2010) Comprehensive Approach to Analyzing Rare Genetic Variants. PloS One 5: 124-137.
27. Pritchard JK, Rosenberg NA, (1999) Use of unlinked genetic markers to detect population stratification in association studies. Am. J. Hum. Genet. 65: 220-228.
28. Marchini J, Cardon LR, Phillips MS, Donnelly P, (2004) The effects of human population structure on large genetic association studies. Nat Genet 36: 512-517.
29. Rosenberg NA, Nordborg M, (2006) A General Population-Genetic Model for the Production by Population Structure of Spurious Genotype-Phenotype Associations in Discrete, Admixed or Spatially Distributed Populations. Genetics 173: 1665-1678.
30. Schaffner SF, Foo C, Gabriel S, Reich D, Daly MJ, et al. (2005) Calibrating a coalescent simulation of human genome sequence variation. Genome Res 15: 1576-1583.
31. Li JZ, Absher DM, Tang H, Southwick AM, Casto AM, et al. (2008) Worldwide human relationships inferred from genome-wide patterns of variation. Science 319: 1100-1104.
32. Biswas S, Scheinfeldt LB, Akey JM, (2009) Genome-wide insights into the patterns and determinants of fine-scale population structure in humans. Am J Hum Genet 84: 641-650.
33. Ewing G, Hermisson J, (2010) MSMS: a coalescent simulation program including recombination, demographic structure and selection at a single locus. Bioinformatics 26: 2064-2065.
34. Peloso G, Lunetta K, (2011) Choice of population structure informative principal components for adjustment in a case-control study. BMC Genet 12: 64 doi:10.1186/1471-2156-12-64.
35. Cardon LR, Palmer LJ, (2003) Population stratification and spurious allelic association. Lancet 361: 598-604.
36. Zondervan KT, Cardon LR, Kennedy SH, (2002) What makes a good case-control study? Hum Reprod 17: 1415-1423.
37. Boyle P, Ferlay J, (2005) Cancer incidence and mortality in Europe, 2004. Ann Oncol 16: 481-488.
38. Fleming DM, Schellevis FG, van Casteren V, (2004) The prevalence of known diabetes in eight European countries. Eur J Public Health 14: 10-14.
39. Farrell PM, (2008) The prevalence of cystic fibrosis in the European Union. J Cyst Fibros 7: 450-453.