One genome-wide significant association, FNBP1L, was reported with fluid intelligence from a gene-based test for association27. FNBP1L (previously known as Toca-1) binds to both CDC42 and WASL, promoting CDC42-induced actin polymerization by activating the N-WASP-WIP complex (15), and is thus implicated in a pathway that links cell surface signals to the actin cytoskeleton, a system that allows the movement of cells and cellular processes. FNBP1L is strongly expressed in neurons, including hippocampal neurons, in developing brains and regulates neuronal morphology. The genome-wide significance threshold for the gene-based test is different to that for the SNP-based test because fewer hypotheses were tested (~17,800). This result did not replicate in the NCNG sample; however, the sample size of the validation cohort was much smaller than the discovery set and it will be necessary to attempt replication of this finding in larger samples before pursuing it further.
