Statistics and Its Interface

Volume 3 (2010)

Number 4

Design cost-effective genome-wide and candidate gene association studies of mother-child pairs

Pages: 543 – 555

DOI: http://dx.doi.org/10.4310/SII.2010.v3.n4.a12

Authors

Jinbo Chen (Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Penn., U.S.A.)

Yun Lu (Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Penn., U.S.A.)

Cuilin Zhang (Division of Epidemiology, Statistics & Prevention Research, National Institute of Child Health and Human Development, Bethesda, Maryland, U.S.A.)

Haitao Zheng (Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Penn., U.S.A.)

Abstract

A case-control mother-child pair design is popular for genetic association studies of obstetric or neonatal outcomes because it allows assessment of both maternal and offspring genotype effects. But a practical constraint is the high genotyping cost, which may double that for a study with the same number of unrelated cases and controls. This issue is particularly relevant for genome-wide association studies, despite the decreasing genotyping cost. Here, we developed cost-effective genotyping strategies for the case-control mother-child pair design. We assumed that the maternal genome had been genotyped $a priori$, and that the primary goal was to detect marginal offspring genotype effects. Our results indicated that only offspring of case mothers needed to be genotyped in order to achieve a statistical power similar to that for screening the maternal genome. Our conclusion was based on a novel score statistic for testing offspring genotype effects that has a higher power than the Armitage trend test.

Keywords

mother-child pairs, maternal genotype effect, offspring genotype effect, one-stage design, two-stage design

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