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24 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6 -1 Responseat[24,-12,-20] -0.5 0 0.5 1 1.5 IMAGS 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6 -1 Responseat[24,-12,-20] -0.5 0 0.5 1 1.5 IMAGS 0 5 10 15 20 25 %contributiontogenecluster contributing loci Cluster P = 0.00008 ADCY8 PRKACG CAMK2G GRIN2B GRIN2A GRM3 PRKCA 25 20 15 10 5 0 GRIN1 GRINA CAMK2A PRKACA PRKAR1A PPP3CB ADCY8 GRIN2A GRM1 CAMK2B PRKACB PRKAR2B PPP3CC CREB1 GRIN2B GRM3 CAMK2D PRKACG MAPK1 PPP1CA CREB3 GRIN2C GRM4 CAMK2G PRKCD MAPK3 PPP1CB CREBBP GRIN2D GRM5 PRKCA PRKCE FYN PPP1CC NCAM1 GRIN3A GRIA1 PRKCB1 PRKCH CALM2 ADCY1 GRIN3B GRIA4 PRKCG PRKAG1 PPP3CA ADCY2 Figure 1. Gene score related to human episodic memory and memory-related brain ac­ tivity. (a) Squares represent a selection of the human homologues of 47 genes with well-­ established molecular and biological functions in synaptic plasticity and/or animal ­memory. Squares in red represent the 7 genes for which significant association of genetic variations with human episodic memory was found. (b) The seven-SNP cluster was used for the cal- culation of an individual›s memory-related genetic score, termed individual memory-asso- ciated genetic score (IMAGS). (c) Regression analysis revealed a significant ­positive cor- relation between the IMAGS and learning-induced brain activations in the ­medial temporal lobe (MTL), including the hippocampus and parahippocampal gyrus. (d) Scatter plot illus- trating the positive correlations between IMAGS and learning-induced brain activations in the hippocampus at coordinate position24, -12, -20 . Adapted from39 . The quest for the ideal statistical methodology We believe that it is impossible to predict which statistical and bioinfor- matics approaches will ideally explain the relationship between genetic and phenotypic variability of such complex traits as episodic memory. It will be most probably a combination of several approaches specific to distinct memory-related phenotypes. The obvious genetic complexity of episodic memory along with studies showing the importance of statisti- 0.80.911. 0.80.911.