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Assessing Disease Risk in Genome-wide Association Studies Using Family History

Ghosh, Arpita; Hartge, Patricia; Purdue, Mark P.; Chanock, Stephen J.; Amundadottir, Laufey; Wang, Zhaoming; Wentzensen, Nicolas; Chatterjee, Nilanjan; Wacholder, Sholom

doi: 10.1097/EDE.0b013e31825583a0

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.

Supplemental Digital Content is available in the text.

From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.

Submitted 14 April 2011; accepted 6 February 2012; posted 9 May 2012.

This study was supported by intramural funding from the National Cancer Institute. The authors reported no other financial interests related to this research.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Arpita Ghosh, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Room 5054, Rockville, MD 20852. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.