/manager/Index ${session.getAttribute("locale")} 5 Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949) /manager/Repository/uon:27386 -9, MIR2113; rs17522122, P=2.55 x 10-8, AKAP6; rs10119, P=5.67 x 10-9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 x 10-6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 x 10-17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.]]> Wed 11 Apr 2018 09:51:21 AEST ]]> GWAS for executive function and processing speed suggests involvement of the CADM2 gene /manager/Repository/uon:23883 P-value=3.12 x 10-8) and in the joint discovery and replication meta-analysis (P-value=3.28 x 10-9 after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 x 10-4). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 x 10-15), gamma-aminobutyric acid (GABA) transport (P-value=1.36 x 10-11) and neuron cell-cell adhesion (P-value=1.48 x 10-13). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.]]> Sat 24 Mar 2018 07:13:41 AEDT ]]>