Concepts and Misconceptions about the Polygenic Additive Model Applied to Disease.

It is nearly one hundred years, since R.A. Fisher published his now famous paper that started the field of quantitative genetics. That paper reconciled Mendelian genetics (as exemplified by Mendel's peas) and the biometrical approach to quantitative traits (as exemplified by the correlation and regression approaches from Galton and Pearson), by showing that a simple model of many genes of small effects, each following Mendel's laws of segregation and inheritance, plus environmental variation could account for the observed resemblance between relatives. In this review, we discuss a number of concepts and misconceptions about the assumptions and limitations of polygenic models of common diseases in human populations.