Detection of Rare Major Genes in Lipid Levels
J. Ott
Human Genetics , 51(1), 79--91 (1979 Sep 2)
Abstract
A statistical test of polygenic inheritance (TPI) against the
alternative of a rare major gene is presented. It is designed for a
random sample of quantitative observations on index cases and
siblings of those index cases (probands) selected on the basis of
the observed measurements of these probands. The test focuses on an
increase of the variance of siblings of probands over its value
under polygenic inheritance, such an increase being expected in the
presence of a major gene producing a shift of the quantitative
observations. Certain data on lipids are then analyzed by this test.
A major gene can tentatively be confirmed for triglycerides but not
for cholesterol. In addition, the values of all index cases are
subjected to an analysis of a mixture of normal distributions
(NOCOMP computer program), resulting in a significant second
component for triglycerides but not for cholesterol. For both TPI
and NOCOMP, the exponent in a power transformation is estimated by
maximum likelihood simultaneously with all other parameters, so that
these analysis methods are robust against a wide range of skewness
in the data, which is demonstrated by manipulation of the
observations and their reanalysis.
