Exceptional Longevity and Polygenic Risk for Cardiovascular Health
by
Mary Revelas 1,2, 
Anbupalam Thalamuthu 1,2
, Christopher Oldmeadow 3, Tiffany-Jane Evans 3, Nicola J. Armstrong 1,4, Carlos Riveros 3,5, John B. Kwok 2,6, Peter R. Schofield 2,6, Henry Brodaty 1,7, Rodney J. Scott 5,8, John R. Attia 3,8, Perminder S. Sachdev 1,9 and Karen A. Mather 1,2,*
Mary Revelas 1,2, Anbupalam Thalamuthu 1,2, Christopher Oldmeadow 3, Tiffany-Jane Evans 3, Nicola J. Armstrong 1,4, Carlos Riveros 3,5, John B. Kwok 2,6, Peter R. Schofield 2,6, Henry Brodaty 1,7, Rodney J. Scott 5,8, John R. Attia 3,8, Perminder S. Sachdev 1,9 and Karen A. Mather 1,2,*
1
Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, NSW 2031, Australia
2
Neuroscience Research Australia, Randwick, NSW 2031, Australia
3
Hunter Medical Research Institute, Newcastle, NSW 2305, Australia
4
Discipline of Mathematics and Statistics, Murdoch University, Perth, WA 6150, Australia
5
Faculty of Health, University of Newcastle, Newcastle, NSW 2308, Australia
6
School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
7
Dementia Centre for Research Collaboration, University of New South Wales, Sydney, NSW 2052, Australia
8
Pathology North, John Hunter Hospital, Newcastle, NSW 2305, Australia
9
Neuropsychiatric Institute, Prince of Wales Hospital, Barker Street, Randwick, NSW 2031, Australia
*
Author to whom correspondence should be addressed.
Genes 2019, 10(3), 227; https://doi.org/10.3390/genes10030227
Received: 31 January 2019 / Revised: 13 March 2019 / Accepted: 14 March 2019 / Published: 18 March 2019
(This article belongs to the Special Issue Genetic Determinants of Human Longevity)
Studies investigating exceptionally long-lived (ELL) individuals, including genetic studies, have linked cardiovascular-related pathways, particularly lipid and cholesterol homeostasis, with longevity. This study explored the genetic profiles of ELL individuals (cases: n = 294, 95–106 years; controls: n = 1105, 55–65 years) by assessing their polygenic risk scores (PRS) based on a genome wide association study (GWAS) threshold of p < 5 × 10−5. PRS were constructed using GWAS summary data from two exceptional longevity (EL) analyses and eight cardiovascular-related risk factors (lipids) and disease (myocardial infarction, coronary artery disease, stroke) analyses. A higher genetic risk for exceptional longevity (EL) was significantly associated with longevity in our sample (odds ratio (OR) = 1.19–1.20, p = 0.00804 and 0.00758, respectively). Two cardiovascular health PRS were nominally significant with longevity (HDL cholesterol, triglycerides), with higher PRS associated with EL, but these relationships did not survive correction for multiple testing. In conclusion, ELL individuals did not have significantly lower polygenic risk for the majority of the investigated cardiovascular health traits. Future work in larger cohorts is required to further explore the role of cardiovascular-related genetic variants in EL.
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MDPI and ACS Style
Revelas, M.; Thalamuthu, A.; Oldmeadow, C.; Evans, T.-J.; Armstrong, N.J.; Riveros, C.; Kwok, J.B.; Schofield, P.R.; Brodaty, H.; Scott, R.J.; Attia, J.R.; Sachdev, P.S.; Mather, K.A. Exceptional Longevity and Polygenic Risk for Cardiovascular Health. Genes 2019, 10, 227.
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