https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index en-au 5 https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:38111 [BI] = 9.38 × 10^-25; p_[SSBI] = 5.23 × 10-14 for hypertension), smoking (p_[BI]= 4.4 × 10^-10; p_[SSBI] = 1.2 × 10^-4), diabetes (p_[BI] = 1.7 × 10 -8; p_[SSBI] = 2.8 × 10^-3), previous cardiovascular disease (p_[BI] = 1.0 × 10^-18; p_[SSBI] = 2.3 × 10^-7), stroke (p_[BI] = 3.9 × 10^-69; p_[SSBI] = 3.2 × 10^-24), and MRI-defined white matter hyperintensity burden (p_[BI]=1.43 × 10^-157; p_[SSBI] = 3.16 × 10^-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p = 0.0022), without indication of directional pleiotropy. Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.]]> Wed 04 Aug 2021 10:54:18 AEST ]]>