Exploration and Comparison of Methods for Combining Population- and Family-based Genetic Association Using the Genetic Analysis Workshop 17 Mini-exome

Overview

Journal BMC Proc

Publisher Biomed Central

Specialty Biology

Date 2012 Mar 1

PMID 22373349

Citations 8

Authors

David W Fardo

Anthony R Druen

Jinze Liu

Lucia Mirea

Claire Infante-Rivard

Patrick Breheny

Affiliations

Soon will be listed here.

Abstract

We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive rates for three existing methods applied to the Genetic Analysis Workshop 17 mini-exome data and compare relative performance. We use knowledge of the underlying data simulation model to make these assessments.

Citing Articles

Sister haplotypes and recombination disequilibrium: a new approach to identify associations of haplotypes with complex diseases.

Liao S, Tan Y Front Genet. 2024; 14:1295327.

PMID: 38292437 PMC: 10825010. DOI: 10.3389/fgene.2023.1295327.

A multiple regression method for genomewide association studies using only linkage information.

Mei B, Wang Z J Genet. 2018; 97(2):477-482.

PMID: 29932068

On combining family- and population-based sequencing data.

Katsumata Y, Fardo D BMC Proc. 2016; 10(Suppl 7):175-179.

PMID: 27980632 PMC: 5133531. DOI: 10.1186/s12919-016-0026-9.

Families or Unrelated: The Evolving Debate in Genetic Association Studies.

Fardo D, Charnigo R, Epstein M J Biom Biostat. 2014; 3(4):e108.

PMID: 25077036 PMC: 4112473.

Haplotype association analysis of combining unrelated case-control and triads with consideration of population stratification.

Wen S, Tsai M Front Genet. 2014; 5:103.

PMID: 24860592 PMC: 4028876. DOI: 10.3389/fgene.2014.00103.

References

Chen Y, Lin H . Simple association analysis combining data from trios/sibships and unrelated controls. Genet Epidemiol. 2008; 32(6):520-7. DOI: 10.1002/gepi.20325. View

Spielman R, McGinnis R, Ewens W . Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993; 52(3):506-16. PMC: 1682161. View

Zhang L, Li J, Pei Y, Liu Y, Deng H . Tests of association for quantitative traits in nuclear families using principal components to correct for population stratification. Ann Hum Genet. 2009; 73(Pt 6):601-13. PMC: 2764806. DOI: 10.1111/j.1469-1809.2009.00539.x. View

Abel L, Muller-Myhsok B . Maximum-likelihood expression of the transmission/disequilibrium test and power considerations. Am J Hum Genet. 1998; 63(2):664-7. PMC: 1377316. DOI: 10.1086/301975. View

Guo C, Lunetta K, DeStefano A, Cupples L . Combined haplotype relative risk (CHRR): a general and simple genetic association test that combines trios and unrelated case-controls. Genet Epidemiol. 2008; 33(1):54-62. PMC: 2700841. DOI: 10.1002/gepi.20356. View

Nagelkerke N, Hoebee B, Teunis P, Kimman T . Combining the transmission disequilibrium test and case-control methodology using generalized logistic regression. Eur J Hum Genet. 2004; 12(11):964-70. DOI: 10.1038/sj.ejhg.5201255. View

Lange C, Silverman E, Xu X, Weiss S, Laird N . A multivariate family-based association test using generalized estimating equations: FBAT-GEE. Biostatistics. 2003; 4(2):195-206. DOI: 10.1093/biostatistics/4.2.195. View

Kazeem G, Farrall M . Integrating case-control and TDT studies. Ann Hum Genet. 2005; 69(Pt 3):329-35. DOI: 10.1046/j.1529-8817.2005.00156.x. View

Vermeulen S, Shi M, Weinberg C, Umbach D . A hybrid design: case-parent triads supplemented by control-mother dyads. Genet Epidemiol. 2008; 33(2):136-44. PMC: 2819841. DOI: 10.1002/gepi.20365. View

10.

Schaid D, Sommer S . Genotype relative risks: methods for design and analysis of candidate-gene association studies. Am J Hum Genet. 1993; 53(5):1114-26. PMC: 1682319. View

11.

Zheng Y, Heagerty P, Hsu L, Newcomb P . On combining family-based and population-based case-control data in association studies. Biometrics. 2010; 66(4):1024-33. PMC: 3038246. DOI: 10.1111/j.1541-0420.2010.01393.x. View

12.

Dudbridge F . Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered. 2008; 66(2):87-98. PMC: 2386559. DOI: 10.1159/000119108. View

13.

Weinberg C, Wilcox A, Lie R . A log-linear approach to case-parent-triad data: assessing effects of disease genes that act either directly or through maternal effects and that may be subject to parental imprinting. Am J Hum Genet. 1998; 62(4):969-78. PMC: 1377041. DOI: 10.1086/301802. View

14.

Joo J, Tian X, Zheng G, Stylianou M, Lin J, Geller N . Joint analysis of case-parents trio and unrelated case-control designs in large scale association studies. BMC Proc. 2008; 1 Suppl 1:S28. PMC: 2367524. DOI: 10.1186/1753-6561-1-s1-s28. View

15.

Almasy L, Dyer T, Peralta J, Kent Jr J, Charlesworth J, Curran J . Genetic Analysis Workshop 17 mini-exome simulation. BMC Proc. 2012; 5 Suppl 9:S2. PMC: 3287854. DOI: 10.1186/1753-6561-5-S9-S2. View

16.

Infante-Rivard C, Mirea L, Bull S . Combining case-control and case-trio data from the same population in genetic association analyses: overview of approaches and illustration with a candidate gene study. Am J Epidemiol. 2009; 170(5):657-64. DOI: 10.1093/aje/kwp180. View

17.

Luedtke A, Powers S, Petersen A, Sitarik A, Bekmetjev A, Tintle N . Evaluating methods for the analysis of rare variants in sequence data. BMC Proc. 2012; 5 Suppl 9:S119. PMC: 3287843. DOI: 10.1186/1753-6561-5-S9-S119. View

18.

Zhu X, Li S, Cooper R, Elston R . A unified association analysis approach for family and unrelated samples correcting for stratification. Am J Hum Genet. 2008; 82(2):352-65. PMC: 2427300. DOI: 10.1016/j.ajhg.2007.10.009. View

19.

Epstein M, Veal C, Trembath R, Barker J, Li C, Satten G . Genetic association analysis using data from triads and unrelated subjects. Am J Hum Genet. 2005; 76(4):592-608. PMC: 1199297. DOI: 10.1086/429225. View

20.

Pfeiffer R, Pee D, Landi M . On combining family and case-control studies. Genet Epidemiol. 2008; 32(7):638-46. PMC: 8336588. DOI: 10.1002/gepi.20338. View