The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data

English version České info

We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study.

Vyšlo v časopise: The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data. PLoS Genet 6(9): e32767. doi:10.1371/journal.pgen.1001096
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001096

Souhrn

Zdroje

1. KolonelLN

HendersonBE

HankinJH

NomuraAM

WilkensLR

2000 A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol 151 346 357

2. RothmanKJ

GreenlandS

1998 Modern Epidemiology Philadelphia Lippincott-Raven

3. ChoiY

WijsmanEM

WeirBS

2009 Case-control association testing in the presence of unknown relationships. Genet Epidemiol 33 668 678

4. RakovskiCS

StramDO

2009 A kinship-based modification of the Armitage trend test to address hidden population structure and small differential genotyping errors. PLoS One 4 e5825 doi:10.1371/journal.pone.0005825

5. AstleW

BaldingDJ

2010 Population structure and cryptic relatedness in genetic association studies. Statistical Science In press

6. ThorntonT

McPeekMS

2010 ROADTRIPS: Case-Control Association Testing with Partially or Completely Unknown Population and Pedigree Structure. Am J Hum Genet 86 172 184

7. BourgainC

HoffjanS

NicolaeR

NewmanD

SteinerL

2003 Novel case-control test in a founder population identifies P-selectin as an atopy-susceptibility locus. Am J Hum Genet 73 612 626

8. PriceAL

PattersonNJ

PlengeRM

WeinblattME

ShadickNA

2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38 904 909

9. CooperRS

TayoB

ZhuX

2008 Genome-wide association studies: implications for multiethnic samples. Hum Mol Genet 17 R151 155

10. CampbellMC

TishkoffSA

2008 African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet 9 403 433

11. BaldingD

NicholsR

1995 A method for quantifying differentiation between populations at multi-allelic locus and its implications for investigating identify and paternity. Genetica 3 3 12

12. DevlinB

RoederK

WassermanL

2001 Genomic control, a new approach to genetic-based association studies. Theoretical Population Biology 60 155 166

13. MarchbanksPA

McDonaldJA

WilsonHG

BurnettNM

DalingJR

2002 The NICHD Women's Contraceptive and Reproductive Experiences Study: methods and operational results. Ann Epidemiol 12 213 221

14. AmbrosoneCB

CiupakGL

BanderaEV

JandorfL

BovbjergDH

2009 Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women. J Oncol 2009 871250

15. JohnEM

SchwartzGG

KooJ

WangW

InglesSA

2007 Sun exposure, vitamin D receptor gene polymorphisms, and breast cancer risk in a multiethnic population. Am J Epidemiol 166 1409 1419

16. JohnEM

HopperJL

BeckJC

KnightJA

NeuhausenSL

2004 The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer. Breast Cancer Res 6 R375 389

17. NewmanB

MoormanPG

MillikanR

QaqishBF

GeradtsJ

1995 The Carolina Breast Cancer Study: integrating population-based epidemiology and molecular biology. Breast Cancer Res Treat 35 51 60

18. ProrokPC

AndrioleGL

BresalierRS

BuysSS

ChiaD

2000 Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Control Clin Trials 21 273S 309S

19. ZhengW

CaiQ

SignorelloLB

LongJ

HargreavesMK

2009 Evaluation of 11 breast cancer susceptibility loci in African-American women. Cancer Epidemiol Biomarkers Prev 18 2761 2764

20. SmithTR

LevineEA

FreimanisRI

AkmanSA

AllenGO

2008 Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis 29 2132 2138

21. NelisM

EskoT

MagiR

ZimprichF

ZimprichA

2009 Genetic structure of Europeans: a view from the North-East. PLoS One 4 e5472 doi:10.1371/journal.pone.0005472

22. LeeAB

LucaD

KleiL

DevlinB

RoederK

2010 Discovering genetic ancestry using spectral graph theory. Genet Epidemiol 34 51 59

23. LucaD

RingquistS

KleiL

LeeAB

GiegerC

2008 On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants. Am J Hum Genet 82 453 463

24. GuanW

LiangL

BoehnkeM

AbecasisGR

2009 Genotype-based matching to correct for population stratification in large-scale case-control genetic association studies. Genet Epidemiol 33 508 517

25. DevlinB

RoederK

1999 Genomic control for association studies. Biometrics 55 997 1004