Familial Associations of Lipid Profiles: A Generalised Estimating Equations Approach

Elevated plasma levels of apolipoproteins A1 (apoA1) and B (apoB)
are important protective factors and risk factors, respectively,
for atherosclerosis and coronary heart disease. It is well known
that both apoA1 and apoB reveal strong familial aggregation. Our
goal was to investigate whether exogenous variables influence these
associations. We used marginal regression models for the mean and
association structure (Generalised Estimating Equations 2; GEE2) to
analyse data from 1435 family members within 469 families of
different sizes included in the Donolo-Tel Aviv Three-Generation
Offspring Study. The usual robust variance matrix was approximated
by extensions of jackknife estimators of variance to GEE2 models.
Upon use of this approach estimation of standard errors in models
with quite complex correlation structures was possible. All
analyses were easily carried out using a menu-driven stand-alone
software tool for marginal regression modelling. We demonstrate
that a variety of hypotheses can be tested using Wald statistics by
modelling regression matrices for the association structure. We
show that correlation for apoB between parent-offspring pairs
increased with decreasing age difference and that pairs with
individuals of the same gender had more similar apoA1 levels than
individuals of different gender. Associations between different
relative pairs did not all agree with those expected from
differences in kinship coefficients. The analysis using GEE2 models
revealed structures that would not have been detected by other
models and should therefore be used in addition to traditional
approaches of analysing family data. GEE2 should be considered a
standard method for the investigation of familial aggregation. [
Published in: Statistics in Medicine 19, Issue 24, 3345-3357 ]