On family-based genome-wide association studies with large pedigrees: Observations and recommendations

David W. Fardo; Xue Zhang; Lili Ding; Hua He; Brad Kurowski; Eileen S. Alexander; Tesfaye B. Mersha; Valentina Pilipenko; Leah Kottyan; Kannabiran Nandakumar; Lisa Martin

doi:10.1186/1753-6561-8-S1-S26

On family-based genome-wide association studies with large pedigrees: Observations and recommendations

David W. Fardo, Xue Zhang, Lili Ding, Hua He, Brad Kurowski, Eileen S. Alexander, Tesfaye B. Mersha, Valentina Pilipenko, Leah Kottyan, Kannabiran Nandakumar, Lisa Martin

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Family based association studies are employed less often than case-control designs in the search for disease-predisposing genes. The optimal statistical genetic approach for complex pedigrees is unclear when evaluating both common and rare variants. We examined the empirical power and type I error rates of 2 common approaches, the measured genotype approach and family-based association testing, through simulations from a set of multigenerational pedigrees. Overall, these results suggest that much larger sample sizes will be required for family-based studies and that power was better using MGA compared to FBAT. Taking into account computational time and potential bias, a 2-step strategy is recommended with FBAT followed by MGA.

Original language	English
Article number	S26
Journal	BMC Proceedings
Volume	8
DOIs	https://doi.org/10.1186/1753-6561-8-S1-S26
State	Published - Jun 17 2014

Bibliographical note

Publisher Copyright:
© 2014 Fardo et al.; licensee BioMed Central Ltd.

Funding

We are grateful to Dr. Patrick Breheny for useful discussion and the anonymous reviewers whose suggestions improved the manuscript. This work was supported in part by NIH grants 8P20GM103436-12 (DWF, KN), K25AG043546 (DWF), NS36695 (LD, LJM), AI070235 (HH, LJM, TBM), AI066738 (LJM), HL111459 (LJM, VP), T32-ES10957 (ESA), K12 HD001097-16 (BGK), K01HL103165 (TBM). The GAW18 whole genome sequence data were provided by the T2D-GENES Consortium, which is supported by NIH grants U01 DK085524, U01 DK085584, U01 DK085501, U01 DK085526, and U01 DK085545. The other genetic and phenotypic data for GAW18 were provided by the San Antonio Family Heart Study and San Antonio Family Diabetes/Gallbladder Study, which are supported by NIH grants P01 HL045222, R01 DK047482, and R01 DK053889. The Genetic Analysis Workshop is supported by NIH grant R01 GM031575. This article has been published as part of BMC Proceedings Volume 8 Supplement 1, 2014: Genetic Analysis Workshop 18. The full contents of the supplement are available online at http://www.biomedcentral.com/bmcproc/ supplements/8/S1. Publication charges for this supplement were funded by the Texas Biomedical Research Institute.

Funders	Funder number
National Institutes of Health (NIH)	8P20GM103436-12, AI066738, AI070235, NS36695, K25AG043546, T32-ES10957, HL111459
Texas Biomedical Research Institute
European Space Agency	K12 HD001097-16, U01 DK085584, R01 DK047482, U01 DK085524, U01 DK085501, U01 DK085545, K01HL103165, P01 HL045222, R01 DK053889, R01 GM031575, U01 DK085526

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1186/1753-6561-8-S1-S26

Cite this

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abstract = "Family based association studies are employed less often than case-control designs in the search for disease-predisposing genes. The optimal statistical genetic approach for complex pedigrees is unclear when evaluating both common and rare variants. We examined the empirical power and type I error rates of 2 common approaches, the measured genotype approach and family-based association testing, through simulations from a set of multigenerational pedigrees. Overall, these results suggest that much larger sample sizes will be required for family-based studies and that power was better using MGA compared to FBAT. Taking into account computational time and potential bias, a 2-step strategy is recommended with FBAT followed by MGA.",

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AU - Kurowski, Brad

AU - Alexander, Eileen S.

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On family-based genome-wide association studies with large pedigrees: Observations and recommendations

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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