Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins

Author:

Wong Matthew WK1ORCID,Thalamuthu Anbupalam1,Braidy Nady1,Mather Karen A12,Liu Yue1,Ciobanu Liliana13,Baune Bernhardt T3456,Armstrong Nicola J7ORCID,Kwok John8,Schofield Peter29,Wright Margaret J1011ORCID,Ames David1213,Pickford Russell14,Lee Teresa115,Poljak Anne1914,Sachdev Perminder S115ORCID

Affiliation:

1. Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia

2. Neuroscience Research Australia, Sydney, Australia

3. The University of Adelaide, Adelaide Medical School, Discipline of Psychiatry, Adelaide, Australia

4. Department of Psychiatry, University of Münster, Münster, Germany

5. Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia

6. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia

7. Mathematics and Statistics, Murdoch University, Perth, Australia

8. Brain and Mind Centre, The University of Sydney, Sydney, Australia

9. School of Medical Sciences, University of New South Wales, Sydney, Australia

10. Queensland Brain Institute, University of Queensland, Brisbane, Australia

11. Centre for Advanced Imaging, University of Queensland, Brisbane, Australia

12. University of Melbourne Academic Unit for Psychiatry of Old Age, Kew, Australia

13. National Ageing Research Institute, Parkville, Australia

14. Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia

15. Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Sydney, Australia

Abstract

The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h2 = 0.28–0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.

Funder

National Health and Medical Research Council

Australian Research Council

Rebecca L. Cooper Medical Research Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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