High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile

M Revelas; A Thalamuthu; A Zettergren; C Oldmeadow; J Najar; NM Seidu; NJ Armstrong; C Riveros; JB Kwok; PR Schofield; JN Trollor; M Waern; MJ Wright; H Zetterberg; D Ames; K Belnnow; H Brodaty; RJ Scott; I Skoog; JR Attia; PS Sachdev; KA Mather

Journal article

High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile

M Revelas, A Thalamuthu, A Zettergren, C Oldmeadow, J Najar, NM Seidu, NJ Armstrong, C Riveros, JB Kwok, PR Schofield, JN Trollor, M Waern, MJ Wright, H Zetterberg, D Ames, K Belnnow, H Brodaty, RJ Scott, I Skoog, JR Attia Show all

Geroscience | Published : 2023

DOI: 10.1007/s11357-022-00643-y

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Abstract

Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual’s polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40–69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55–85 years), Older Australian Twins Study (n = 539, 65–..

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University of Melbourne Researchers

David Ames Author

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Funding Acknowledgements

Open Access funding enabled and organized by CAUL and its Member Institutions The UK Biobank is funded primarily by the Wellcome Charity and the Medical Research Council (MRC), all details of funds awarded to the UKBB can be viewed at https://www.ukbiobank.ac.uk/wp-content/uploa ds/2018/10/Funding-UK-Biobanksummary.pdf. This research has been conducted using the UKBB resource (Application Number 53850). The Hunter Community Study would like to acknowledge the support of the University of Newcastle and the Fairfax Family Foundation. The OATS study has been funded by a National Health & Medical Research Council (NHMRC) and Australian Research Council (ARC) Strategic Award Grant of the Ageing Well, Ageing Productively Program (ID No. 401162); NHMRC Project (seed) Grants (ID No. 1024224 and 1025243); NHMRC Project Grants (ID No. 1045325 and 1085606); and NHMRC Program Grants (ID No. 568969 and 1093083). This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (ID No. 1079102) from the National Health and Medical Research Council. The NHMRC Program Grants 350833, 568969 and 109308, support the Sydney Memory and Ageing Study. AZ is supported by the Swedish Alzheimer Foundation (AF-939988, AF-930582), Stiftelsen Demensfonden, and Magnus Bergvalls Stiftelse.MW is supported by the Swedish Research Council (2016-01590), the Swedish Research Council for Health, Working Life and Welfare (2016-07097). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (2018-02532), the European Research Council (681712), Swedish State Support for Clinical Research (ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (201809-2016862), the AD Strategic Fund and the Alzheimer's Association (ADSF21-831376-C, ADSF-21-831381-C and ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen for Gamla Tjanarinnor, Hjarnfonden, Sweden (FO2019-0228), the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 860197 (MIRIADE), and the UK Dementia Research Institute at UCL.KB is supported by the Swedish Research Council (2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (RDAPB-201809-2016615), the Swedish Alzheimer Foundation (AF-742881), Hjarnfonden, Sweden (FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the National Institute of Health (NIH), USA, (grant 1R01AG068398-01), and the Alzheimer's Association 2021 Zenith Award (ZEN-21-848495). IS is supported by the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALF 716681), the Swedish Research Council (no 11267, 825-20125041, 2013-8717, 2015-02830, 2017-00639, 2019-01096), Swedish Research Council for Health, Working Life and Welfare (no 2001-2646, 2001-2835, 2001-2849, 2003-0234, 2004-0150, 2005-0762, 2006-0020, 2008-1229, 2008-1210, 2012-1138, 2004-0145, 2006-0596, 2008-1111, 2010-0870, 2013-1202, 2013-2300, 2013-2496), Swedish Brain Power, Hjarnfonden, Sweden (FO2016-0214, FO2018-0214, FO20190163), the Alzheimer's Association Zenith Award (ZEN-013151), the Alzheimer's Association Stephanie B. Overstreet Scholars (IIRG-00-2159), the Alzheimer's Association (IIRG03-6168, IIRG-09-131338) and the Bank of Sweden Tercentenary Foundation.