Heritability of Gene Expression measured from Peripheral Blood in Older Adults

Author:

Kanchibhotla Sri C.1,Mather Karen A.1,Armstrong Nicola J.2,Ciobanu Liliana G3,Baune Bernhard T.3,Catts Vibeke S1,Schofield Peter R.4,Trollor Julian N.1,Ames David5,Sachdev Perminder S.1,Thalamuthu Anbupalam1

Affiliation:

1. University of New South Wales

2. Curtin University

3. The University of Adelaide

4. Neuroscience Research Australia

5. The University of Melbourne

Abstract

Abstract The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of gene expression from peripheral blood 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 monozygotic (MZ) and 52 dizygotic (DZ) twin pairs, 69.91% females) with a mean age of 75.79 (S.D. = 5.44) were studied. RNA was extracted from peripheral blood and gene expression assessed using Illumina microarrays. Heritability (h2) analysis was performed using structural equation modelling. Out of the available 26537 probes (19256 genes) there were 5269 probes (19.9%) from 4603 unique genes (23.9%) that were significantly heritable, with a mean moderate heritability (h2 = 0.40). The gene, ERAP2, showed the highest heritability (h2 = 0.87; FDR = 2.91E-22). Pathway analysis of the top 10% of significant genes showed enrichment for the immune response, longevity 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.

Publisher

Research Square Platform LLC

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