A General Efficient and Flexible Approach for Genome‐Wide Association Analyses of Imputed Genotypes in Family‐Based Designs |
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| Authors: | Aurélie Cobat Laurent Abel Erwin Schurr |
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| Affiliation: | 1. Departments of Human Genetics and Medicine, McGill International TB Center, McGill University Health Center, Montreal, QC, Canada;2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France;3. Sorbonne Paris Cité, Imagine Institute, University Paris Descartes, Paris, France;4. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America |
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| Abstract: | ![]()
Genotype imputation is a critical technique for following up genome‐wide association studies. Efficient methods are available for dealing with the probabilistic nature of imputed single nucleotide polymorphisms (SNPs) in population‐based designs, but not for family‐based studies. We have developed a new analytical approach (FBATdosage), using imputed allele dosage in the general framework of family‐based association tests to bridge this gap. Simulation studies showed that FBATdosage yielded highly consistent type I error rates, whatever the level of genotype uncertainty, and a much higher power than the best‐guess genotype approach. FBATdosage allows fast linkage and association testing of several million of imputed variants with binary or quantitative phenotypes in nuclear families of arbitrary size with arbitrary missing data for the parents. The application of this approach to a family‐based association study of leprosy susceptibility successfully refined the association signal at two candidate loci, C1orf141‐IL23R on chromosome 1 and RAB32‐C6orf103 on chromosome 6. |
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| Keywords: | Family‐based association test genetic imputation genome‐wide association studies leprosy |
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