A Parent-Informed Test for the X-Chromosome Using Case-Parent Triads

• Activity Number: 353
• Type: Contributed
• Date/Time: Tuesday, August 5, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Alison Wise*+ and Clarice Weinberg and Min Shi
• Companies: NIEHS/University of North Carolina at Chapel Hill and NIEHS and National Institute of Environmental Health Sciences
• Keywords: case-parent trios ; family-based association ; X-linked ; X-chromosome ; linkage disequilibrium

Abstract

The X-chromosome is generally understudied in association studies because the analyst has limited methodological options. For family-based association studies, most current methods extend the transmission disequilibrium test (TDT) to the X-chromosome. We present a new method to study association in case-parent triads: the parent-informed likelihood ratio test for the X-chromosome (PIX-LRT). Our method takes advantage of parental genotype information and the sex of the affected offspring to increase statistical power to detect an effect. Our method is able to estimate relative risks of alleles under different modes of inheritance or a more general co-dominant model. In triads with missing parental genotypes, our method accounts for this missingness with the EM algorithm. We calculate non-centrality parameters to demonstrate the power gain and relative robustness of our method compared to current methods. We apply PIX-LRT to publically available data from an international consortium of genotyped families affected by the birth defect oral cleft and identify a novel SNP marker related to cleft lip with or without cleft palate.