X-LRT: A likelihood approach to estimate genetic risks and test association with X-linked markers using a case-parents design

Li Zhang, Eden R. Martin, Ren Hua Chung, Yi Ju Li, Richard W. Morris

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)370-380
Number of pages11
JournalGenetic Epidemiology
Volume32
Issue number4
DOIs
StatePublished - May 1 2008

Keywords

  • Confidence interval
  • Family-based design
  • Hypothesis test
  • Maximum-likelihood estimation
  • Sex linked

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

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