Weaknesses of familial aggregation and segregation analyses

While most of these studies included measures of
personal smoking on the cases (or probands) and
controls in the models, some of the aggregation
studies did not include measures of amount of
cigarette smoking in the relatives and only one in-
cluded measures of passive smoking. The segrega-
tion analyses did not include passive smoking or oc-
cupational risk factors in the models, and only one
of these three studies collected data on history of
chronic bronchitis. Furthermore, segregation anal-
yses are not sufficient to prove the existence of a
major locus because only a subset of all possible
models can be tested. These segregation analyses
did not, for example, model the large number of
possible oligogenic cases where two or three major
loci act in conjunction with smoking to affect risk of
lung cancer.