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A unified framework for transmission‐disequilibrium test analysis of discrete and continuous traits
Author(s) -
Liu Ying,
Tritchler David,
Bull Shelley B.
Publication year - 2002
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.1041
Subject(s) - kurtosis , exponential family , covariate , test statistic , disequilibrium , statistics , mathematics , statistic , type i and type ii errors , transmission disequilibrium test , polygene , major gene , skewness , biology , statistical hypothesis testing , econometrics , genetics , quantitative trait locus , gene , haplotype , medicine , genotype , ophthalmology
This paper presents a unified framework for transmission‐disequilibrium tests for discrete and continuous traits. A conditional score test is derived that maximizes power to detect small effects for any exponential family distribution, which includes binary and normal distributions, and distributions that are skewed or have non‐normal kurtosis. The specific distributional form need not be specified, and the method applies to sibships of arbitrary size. Formulas for the distribution of the test statistic are given for models including complex genetic effects (additive, dominant, and recessive gene action), covariates, multiple gene models including gene‐gene interactions or heterogeneity, and gene‐environment interactions. We develop refinements of our method for trait‐based sampling designs and multiple siblings that can have dramatic effects on power. Genet. Epidemiol. 22:26–40, 2002. © 2002 Wiley‐Liss, Inc.