Heritability of Gene Expression Measured from Peripheral Blood in Older Adults

Author:

Kanchibhotla Sri C.1,Mather Karen A.12,Armstrong Nicola J.3ORCID,Ciobanu Liliana G.4,Baune Bernhard T.4567,Catts Vibeke S.1,Schofield Peter R.28ORCID,Trollor Julian N.19ORCID,Ames David1011,Sachdev Perminder S.112ORCID,Thalamuthu Anbupalam1ORCID

Affiliation:

1. Centre for Healthy Brain Ageing, Discipline of Psychiatry & Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia

2. Neuroscience Research Australia, Sydney, NSW 2031, Australia

3. Department of Mathematics and Statistics, Curtin University, Perth, WA 6845, Australia

4. Discipline of Psychiatry, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia

5. Department of Psychiatry, University of Münster, 48149 Münster, Germany

6. Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, VIC 3052, Australia

7. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia

8. School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia

9. Department of Developmental Disability Neuropsychiatry, Discipline of Psychiatry & Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia

10. Academic Unit for Psychiatry of Old Age, University of Melbourne, St George’s Hospital, Kew, Melbourne, VIC 3010, Australia

11. National Ageing Research Institute, Parkville, VIC 3052, Australia

12. Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Sydney, NSW 2031, Australia

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 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.

Funder

Australian Research Council (ARC) Strategic Award Grant of the Ageing Well, Ageing Productively Program

NHMRC Project

NHMRC Program

Centre of Research Excellence

NHMRC

Publisher

MDPI AG

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