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X‐LRT: a likelihood approach to estimate genetic risks and test association with X‐linked markers using a case‐parents design
Author(s) -
Zhang Li,
Martin Eden R.,
Chung RenHua,
Li YiJu,
Morris Richard W.
Publication year - 2008
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20311
Subject(s) - penetrance , proband , pedigree chart , genetics , type i and type ii errors , genetic association , association test , biology , nuclear family , likelihood ratio test , score test , statistics , genotype , mathematics , gene , mutation , sociology , single nucleotide polymorphism , anthropology , phenotype
Abstract Recently, there has been interest in family‐based tests of association to identify X‐chromosome genes. However, none of the approaches allow for estimation of genetic risks. We propose a likelihood approach to estimate disease‐related marker relative risks and test genotype association using a case‐parents design. The test uses nuclear families with a single affected proband and allows additional siblings and missing parental genotypes. Extension to a haplotype test is based on assumptions of random mating and multiplicative penetrance. We investigate power and type I error rate of the likelihood‐based test, using simulated data and apply our method to marker data from the monoamine oxidase A&B genes in families with Parkinson disease. We show how efficiency with missing parental information can be improved with additional sibling genotype information. Our likelihood approach offers great flexibility for testing different penetrance relationships within and between sexes. In addition, estimation of disease‐related marker relative risks provides a measure of the magnitude of X‐linked genetic effects on complex disorders. Genet. Epidemiol . 2008. © 2008 Wiley‐Liss, Inc.