https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30988 2 and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants. Results: The models including environmental risk factors only had pseudo R² values of 16.5–28.3% and AUC of 0.75–0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10⁻⁴–4.83 × 10⁻¹²) and increased the pseudo R² by about 1–2% and AUC by 1–3%. None of the gene–environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 < P < 0.05. Conclusion: This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene–environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection.]]> Wed 23 Feb 2022 16:06:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21916 Wed 10 Jul 2019 15:18:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /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.]]> Thu 13 Jan 2022 10:29:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21864 Sat 24 Mar 2018 07:59:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27574 Sat 24 Mar 2018 07:23:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22849 P < 0.001) and 34% (±10%, P < 0.001), respectively. Conclusions: Our data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.]]> Sat 24 Mar 2018 07:16:02 AEDT ]]>