Premium
Detection of vulnerability loci by association and sib‐pair methods
Author(s) -
Levinson Douglas F.
Publication year - 1995
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.1370120618
Subject(s) - linkage disequilibrium , bonferroni correction , locus (genetics) , haplotype , genetics , biology , disequilibrium , allele , transmission disequilibrium test , multiple comparisons problem , statistics , evolutionary biology , mathematics , gene , medicine , ophthalmology
A haplotype‐based haplotype relative risk (HHRR) analysis of simulated data for 200 affected offspring and their parents (Genetic Analysis Workshop 9, Problem 1) detected linkage disequilibrium at 2 of 360 marker loci. An additive model was suggested but not proven by haplotypes of affected vs. unaffected offspring. These findings were consistent with the generating model. Affected sib pair analysis failed to detect additional loci. Discussion among workshop participants suggested that the chi‐square test used here (2 [transmitted vs. nontransmitted] x n [alleles] for each locus) was invalid because of the nonindependence of proportions of transmitted alleles. In post‐workshop analyses, transmission disequilibrium tests (TDTs) for each allele at each locus detected only the true associations if p values were corrected by one of two methods: Bonferroni correction for 2,035 TDTs, or correcting each test for n (number of tests at the locus) minus 1 and then for the number of loci tested. Screening loci for linkage disequilibrium requires careful attention to correction for multiple comparisons. ©1995 Wiley‐Liss, Inc.