Early association studies of DZ twinning were with obvious candidate genes, including those for peptide hormones known to be involved in reproduction (FSHB, FSHR, LHB, inhibins, GNRH and FST) as well as less obvious ones including the fragile-X syndrome gene FRAXA, PPARG and MTHFR. As with candidate gene studies in most other complex traits, results have been mixed and only few replicable associations have been found. Many of these studies were also statistically underpowered given current ideas of gene effect sizes.
It is now clearly necessary to take a more global approach to this problem, using genome wide association (GWAS) with a very large population to obtain adequate statistical power.
