Heritability of Gene Expression Measured from Peripheral Blood in Older Adults.

The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ twins, 69.91% females; mean age-75.79 ± 5.44) were studied. Peripheral blood gene expression was assessed using Illumina microarrays. A heritability analysis was performed using structural equation modelling. There were 5269 probes (19.9%) from 4603 unique genes (23.9%) (total 26,537 probes from 19,256 genes) that were significantly heritable (mean h2 = 0.40). A pathway analysis of the top 10% of significant genes showed enrichment for the immune response and ageing-associated genes. In a comparison with two other gene expression twin heritability studies using adults from across the lifespan, there were 38 out of 9479 overlapping genes that were significantly heritable. In conclusion, our study found ~24% of the available genes for analysis were heritable in older adults, with only a small number common across studies that used samples from across adulthood, indicating the importance of examining gene expression in older age groups.

Genetics of microstructure of the corpus callosum in older adults.

The current study sought to examine the relative influence of genetic and environmental factors on corpus callosum (CC) microstructure in a community sample of older adult twins. Analyses were undertaken in 284 healthy older twins (66% female; 79 MZ and 63 DZ pairs) from the Older Australian Twins Study. The average age of the sample was 69.82 (SD = 4.76) years. Brain imaging scans were collected and DTI measures were estimated for the whole CC as well as its five subregions. Parcellation of the CC was performed using Analyze. In addition, white matter lesion (WMLs) burden was estimated. Heritability and genetic correlation analyses were undertaken using the SOLAR software package. Age, sex, scanner, handedness and blood pressure were considered as covariates. Heritability (h(2)) analysis for the DTI metrics of whole CC, indicated significant h(2) for fractional anisotropy (FA) (h(2) = 0.56; p = 2.89×10(-10)), mean diffusivity (MD) (h(2) = 0.52; p = 0.30×10(-6)), radial diffusivity (RD) (h(2) = 0.49; p = 0.2×10(-6)) and axial diffusivity (AD) (h(2) = 0.37; p = 8.15×10(-5)). We also performed bivariate genetic correlation analyses between (i) whole CC DTI measures and (ii) whole CC DTI measures with total brain WML burden. Across the DTI measures for the whole CC, MD and RD shared 84% of the common genetic variance, followed by MD-AD (77%), FA-RD (52%), RD-AD (37%) and FA-MD (11%). For total WMLs, significant genetic correlations indicated that there was 19% shared common genetic variance with whole CC MD, followed by CC RD (17%), CC AD (16%) and CC FA (5%). Our findings suggest that the CC microstructure is under moderate genetic control. There was also evidence of shared genetic factors between the CC DTI measures. In contrast, there was less shared genetic variance between WMLs and the CC DTI metrics, suggesting fewer common genetic variants.

Genetics of ageing-related changes in brain white matter integrity - a review.

White matter (WM) plays a vital role in the efficient transfer of information between grey matter regions. Modern imaging techniques such as diffusion tensor imaging (DTI) have enabled the examination of WM microstructural changes across the lifespan, but there is limited knowledge about the role genetics plays in the pattern and aetiology of age-related WM microstructural changes. Family and twin studies suggest that the heritability of WM integrity measures changes over the lifespan, with the common DTI measure, fractional anisotropy (FA), showing moderate to high heritability in adults. However, few heritability studies have been undertaken in older adults. Linkage studies in middle-aged adults suggest that specific regions on chromosomes 3 and 15 may harbour genetic variants for WM integrity. A number of studies have investigated candidate genes, with the APOE ɛ4 polymorphism being the most frequently studied. Although these candidate gene studies suggest associations of particular genes with WM integrity measures in some specific brain regions, the findings remain inconsistent due to differences in their methodologies, samples and the outcome measures used. The APOE ɛ4 allele has been associated with decreased WM integrity (FA) in the cingulum, corpus callosum and parahippocampal gyrus. Only one genome-wide association study of global WM integrity measures in older adults has been published, and reported suggestive single nucleotide polymorphisms await replication. Overall, genetic age-related WM integrity studies are lacking and a concerted effort to examine the genetic determinants of age-related decline in WM integrity is clearly needed to improve our understanding of the ageing brain.