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Genes 2019, 10(3), 227;

Exceptional Longevity and Polygenic Risk for Cardiovascular Health

Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, NSW 2031, Australia
Neuroscience Research Australia, Randwick, NSW 2031, Australia
Hunter Medical Research Institute, Newcastle, NSW 2305, Australia
Discipline of Mathematics and Statistics, Murdoch University, Perth, WA 6150, Australia
Faculty of Health, University of Newcastle, Newcastle, NSW 2308, Australia
School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Dementia Centre for Research Collaboration, University of New South Wales, Sydney, NSW 2052, Australia
Pathology North, John Hunter Hospital, Newcastle, NSW 2305, Australia
Neuropsychiatric Institute, Prince of Wales Hospital, Barker Street, Randwick, NSW 2031, Australia
Author to whom correspondence should be addressed.
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)
PDF [1223 KB, uploaded 27 March 2019]


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. View Full-Text
Keywords: polygenic risk score; cardiovascular health; exceptional longevity; lipid profile polygenic risk score; cardiovascular health; exceptional longevity; lipid profile

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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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