X-LRT: a likelihood approach to estimate genetic risks and test association with X-linked markers using a case-parents design.
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.
Zhang
Li
L
Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA.
Martin
Eden R
ER
Chung
Ren-Hua
RH
Li
Yi-Ju
YJ
Morris
Richard W
RW
D000465:Algorithms; D001699:Biometry; D003198:Computer Simulation; D016001:Confidence Intervals; D004812:Epidemiologic Methods; D005260:Female; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000453:epidemiology / Q000235:genetics*; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008957:Models, Genetic; D008995:Monoamine Oxidase / Q000235:genetics; D010290:Parents; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics; D019683:Penetrance; D012307:Risk Factors; D035781:Siblings
D005819:Genetic Markers; D008995:Monoamine Oxidase