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Validity, efficiency, and robustness of a family‐based test of association
Author(s) -
Lewinger Juan Pablo,
Bull Shelley B.
Publication year - 2006
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.20125
Subject(s) - population stratification , statistics , robustness (evolution) , score test , test statistic , statistic , association test , type i and type ii errors , genetic association , population , mathematics , statistical power , allele , statistical hypothesis testing , econometrics , genetics , biology , genotype , demography , single nucleotide polymorphism , sociology , gene
We propose a new test of linkage in the presence of allelic association that uses all available information in a sample of nuclear families, including parental phenotypes, genotypes from both affected and unaffected siblings, and families with homozygous parents. The test is based on the conditional framework developed by Rabinowitz and Laird [2000: Hum Hered 50:211–223] and is thus immune to population stratification and can be applied to families with any pattern of missing information. The test statistic is a conditional likelihood ratio based on a standard two‐point linkage model with allelic association, where parameters are estimated from the sample. Through a simulation study, we determined that the proposed test has near optimal power for a wide range of scenarios, outperforming FBAT both when data were complete and when parental genotypes were missing, although differences between the two tests diminish as the genetic effect is reduced. To assess robustness, we also evaluated the performance of the tests under scenarios with population stratification and found that although there is a loss of efficiency, our proposed test remains a strong competitor to FBAT. Genet. Epidemiol . 30:62‐76, 2006. © 2005 Wiley‐Liss, Inc.