found that sets of SNPs of nominal significance might be used to identify genomic regions that are over-represented across independent GWAS97, 98—here as well, cell-adhesion genes, such as cadherins, are prominent, although only nominally significant in the individual studies. Although it is not possible to distinguish true signals from false positives with current sample sizes, we can be certain that even among SNPs that are less significantly associated, there are many SNPs that do influence the traits under study. Using a regression approach that simultaneously examines the contribution of all GWAS variants, Visscher and colleagues95 have shown that 43, 17 and 54% of total phenotypic variance in height, body mass index99 and intelligence quotient100 respectively, is due to causal variants in linkage disequilibrium with SNPs on commercial GWAS arrays. For height, they further showed that adjusting for imperfect linkage disequilibrium between typed SNPs and causal SNPs raised the estimate to 54%, and further adjustment for the gross under-representation of rare SNPs on commercial chips, raised the estimate to 70–80%, close to estimates of heritability of height from conventional twin and family studies. Such efforts are currently under way for studies of addiction.
