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 journalArticlepeer-review

2 Scopus citations


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
Issue number2
StatePublished - Feb 2014
Externally publishedYes


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

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)


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