Leveraging Family History in Population-Based Case-Control Association Studies

Arpita Ghosh, Patricia Hartge, Peter Kraft, Amit D. Joshi, Regina G. Ziegler, Myrto Barrdahl, Stephen J. Chanock, Sholom Wacholder, Nilanjan Chatterjee

Research output: Contribution to journalArticle

Abstract

Population-based epidemiologic studies often gather information from study participants on disease history among their family members. Although investigators widely recognize that family history will be associated with genotypes of the participants at disease susceptibility loci, they commonly ignore such information in primary genetic association analyses. In this report, we propose a simple approach to association testing by incorporating family history information as a "phenotype." We account for the expected attenuation in strength of association of the genotype of study participants with family history under Mendelian transmission. The proposed analysis can be performed using standard statistical software adopting either a meta- or pooled-analysis framework. Re-analysis of a total of 115 known susceptibility single-nucleotide polymorphisms, discovered through genome-wide association studies for several disease traits, indicates that incorporation of family history information can increase efficiency by as much as 40%. Efficiency gain depends on the type of design used for conducting the primary study, extent of family history, and accuracy and completeness of reporting.

Original languageEnglish (US)
Pages (from-to)114-122
Number of pages9
JournalGenetic Epidemiology
Volume38
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

Fingerprint

Case-Control Studies
Population
Genotype
Genome-Wide Association Study
Disease Susceptibility
Single Nucleotide Polymorphism
Epidemiologic Studies
Software
Research Personnel
Phenotype

Keywords

  • Disease history in family members
  • First-degree relatives
  • Meta-analysis
  • More powerful test for genetic association

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Ghosh, A., Hartge, P., Kraft, P., Joshi, A. D., Ziegler, R. G., Barrdahl, M., ... Chatterjee, N. (2014). Leveraging Family History in Population-Based Case-Control Association Studies. Genetic Epidemiology, 38(2), 114-122. https://doi.org/10.1002/gepi.21785

Leveraging Family History in Population-Based Case-Control Association Studies. / Ghosh, Arpita; Hartge, Patricia; Kraft, Peter; Joshi, Amit D.; Ziegler, Regina G.; Barrdahl, Myrto; Chanock, Stephen J.; Wacholder, Sholom; Chatterjee, Nilanjan.

In: Genetic Epidemiology, Vol. 38, No. 2, 02.2014, p. 114-122.

Research output: Contribution to journalArticle

Ghosh, A, Hartge, P, Kraft, P, Joshi, AD, Ziegler, RG, Barrdahl, M, Chanock, SJ, Wacholder, S & Chatterjee, N 2014, 'Leveraging Family History in Population-Based Case-Control Association Studies', Genetic Epidemiology, vol. 38, no. 2, pp. 114-122. https://doi.org/10.1002/gepi.21785
Ghosh A, Hartge P, Kraft P, Joshi AD, Ziegler RG, Barrdahl M et al. Leveraging Family History in Population-Based Case-Control Association Studies. Genetic Epidemiology. 2014 Feb;38(2):114-122. https://doi.org/10.1002/gepi.21785
Ghosh, Arpita ; Hartge, Patricia ; Kraft, Peter ; Joshi, Amit D. ; Ziegler, Regina G. ; Barrdahl, Myrto ; Chanock, Stephen J. ; Wacholder, Sholom ; Chatterjee, Nilanjan. / Leveraging Family History in Population-Based Case-Control Association Studies. In: Genetic Epidemiology. 2014 ; Vol. 38, No. 2. pp. 114-122.
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