title: Assessing disease risk in genome-wide association studies using family history.
abstract: We show how to use reports of cancer in family members to discover additional genetic associations or confirm previous findings in genome-wide association (GWA) studies conducted in case-control, cohort, or cross-sectional studies. Our novel family history-based approach allows economical association studies for multiple cancers, without genotyping of relatives (as required in family studies), follow-up of participants (as required in cohort studies), or oversampling of specific cancer cases (as required in case-control studies). We empirically evaluate the performance of the proposed family history-based approach in studying associations with prostate and ovarian cancers, using data from GWA studies previously conducted within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The family history-based method may be particularly useful for investigating genetic susceptibility to rare diseases for which accruing cases may be very difficult, by using disease information from nongenotyped relatives of participants in multiple case-control and cohort studies designed primarily for other purposes.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852,USA. ghosha3@mail.nih.gov
authors.forename: Arpita
authors.initials: A
authors.lastname: Ghosh
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Laufey
authors.initials: L
authors.lastname: Amundadottir
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D060005:Genotyping Techniques; D006801:Humans; D016015:Logistic Models; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk; D011795:Surveys and Questionnaires