The exponential fall in genome sequencing costs led to the use of genome-wide association studies (GWASes) which could simultaneously examine all candidate-genes in larger samples than the original finding, where the candidate-gene hits were found to almost always be false positives and only 2-6% replicate;[7][8][9][10][11][12] in the specific case of intelligence candidate-gene hits, only 1 candidate-gene hit replicated,[13] the top 25 schizophrenia candidate-genes were no more associated with schizophrenia than chance,[14][15] and of 15 neuroimaging hits, none did.
[16] In 2012, the editorial board of Behavior Genetics noted, in setting more stringent requirements for candidate-gene publications, that "the literature on candidate gene associations is full of reports that have not stood up to rigorous replication...it now seems likely that many of the published findings of the last decade are wrong or misleading and have not contributed to real advances in knowledge".
[17] Other researchers have characterized the literature as having "yielded an infinitude of publications with very few consistent replications" and called for a phase out of candidate-gene studies in favor of polygenic scores.
[18] Standard genetics methods have long estimated large heritabilities such as 80% for traits such as height or intelligence, yet none of the genes had been found despite sample sizes that, while small, should have been able to detect variants of reasonable effect size such as 1 inch or 5 IQ points.
Several resolutions have been proposed, that the missing heritability is some combination of: