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Sweden","award":["09-063256"],"award-info":[{"award-number":["09-063256"]}]},{"name":"the SNP&amp;SEQ Technology Platform, Science for Life Laboratory, Uppsala, Sweden","award":["P01 AG08761"],"award-info":[{"award-number":["P01 AG08761"]}]},{"name":"the SNP&amp;SEQ Technology Platform, Science for Life Laboratory, Uppsala, Sweden","award":["NIH R01 AG037985"],"award-info":[{"award-number":["NIH R01 AG037985"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Longevity is a complex phenotype influenced by both environmental and genetic factors. The genetic contribution is estimated at about 25%. Despite extensive research efforts, only a few longevity genes have been validated across populations. Long-lived individuals (LLI) reach extreme ages with a relative low prevalence of chronic disability and major age-related diseases (ARDs). We tested whether the protection from ARDs in LLI can partly be attributed to genetic factors by calculating polygenic risk scores (PRSs) for seven common late-life diseases (Alzheimer\u2019s disease (AD), atrial fibrillation (AF), coronary artery disease (CAD), colorectal cancer (CRC), ischemic stroke (ISS), Parkinson\u2019s disease (PD) and type 2 diabetes (T2D)). The examined sample comprised 1351 German LLI (\u226594 years, including 643 centenarians) and 4680 German younger controls. For all ARD-PRSs tested, the LLI had significantly lower scores than the younger control individuals (areas under the curve (AUCs): ISS = 0.59, p = 2.84 \u00d7 10\u221235; AD = 0.59, p = 3.16 \u00d7 10\u221225; AF = 0.57, p = 1.07 \u00d7 10\u221216; CAD = 0.56, p = 1.88 \u00d7 10\u221212; CRC = 0.52, p = 5.85 \u00d7 10\u22123; PD = 0.52, p = 1.91 \u00d7 10\u22123; T2D = 0.51, p = 2.61 \u00d7 10\u22123). We combined the individual ARD-PRSs into a meta-PRS (AUC = 0.64, p = 6.45 \u00d7 10\u221215). We also generated two genome-wide polygenic scores for longevity, one with and one without the TOMM40\/APOE\/APOC1 gene region (AUC (incl. TOMM40\/APOE\/APOC1) = 0.56, p = 1.45 \u00d7 10\u22125, seven variants; AUC (excl. TOMM40\/APOE\/APOC1) = 0.55, p = 9.85 \u00d7 10\u22123, 10,361 variants). Furthermore, the inclusion of nine markers from the excluded region (not in LD with each other) plus the APOE haplotype into the model raised the AUC from 0.55 to 0.61. Thus, our results highlight the importance of TOMM40\/APOE\/APOC1 as a longevity hub.<\/jats:p>","DOI":"10.3390\/ijms231810949","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T21:47:27Z","timestamp":1663624047000},"page":"10949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Long-Lived Individuals Show a Lower Burden of Variants Predisposing to Age-Related Diseases and a Higher Polygenic Longevity Score"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-7815","authenticated-orcid":false,"given":"Guillermo G.","family":"Torres","sequence":"first","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janina","family":"Dose","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7028-6559","authenticated-orcid":false,"given":"Tim P.","family":"Hasenbein","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany"},{"name":"Department of Neurology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, 24105 Kiel, Germany"},{"name":"Institute of Pharmacology and Toxicology, Technical University Munich, Biedersteiner Str. 29, 80802 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-2665","authenticated-orcid":false,"given":"Marianne","family":"Nygaard","sequence":"additional","affiliation":[{"name":"Department of Public Health, Epidemiology, Biostatistics and Biodemography, University of Southern, Denmark, J.B. Winsloews Vej 9B, 5000 Odense, Denmark"},{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winsloews Vej 4, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9435-2872","authenticated-orcid":false,"given":"Ben","family":"Krause-Kyora","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1573-8908","authenticated-orcid":false,"given":"Jonas","family":"Mengel-From","sequence":"additional","affiliation":[{"name":"Department of Public Health, Epidemiology, Biostatistics and Biodemography, University of Southern, Denmark, J.B. Winsloews Vej 9B, 5000 Odense, Denmark"},{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winsloews Vej 4, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaare","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Public Health, Epidemiology, Biostatistics and Biodemography, University of Southern, Denmark, J.B. Winsloews Vej 9B, 5000 Odense, Denmark"},{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winsloews Vej 4, 5000 Odense, Denmark"},{"name":"Department of Clinical Biochemistry, Odense University Hospital, Kl\u00f8verv\u00e6nget 47, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Andersen-Ranberg","sequence":"additional","affiliation":[{"name":"Department of Public Health, Epidemiology, Biostatistics and Biodemography, University of Southern, Denmark, J.B. Winsloews Vej 9B, 5000 Odense, Denmark"},{"name":"Department of Geriatric Medicine, Odense University Hospital, Kl\u00f8verv\u00e6nget 23, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Kolbe","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Lieb","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Biobank Popgen, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Niemannsweg 11, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Laudes","sequence":"additional","affiliation":[{"name":"Clinic for Internal Medicine I, Division of Endocrinology, Diabetes and Clinical Nutrition, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Stra\u00dfe 3, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siegfried","family":"G\u00f6rg","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, University Hospital Schleswig-Holstein, Campus L\u00fcbeck, Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amke","family":"Caliebe","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Str. 10, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregor","family":"Kuhlenb\u00e4umer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Almut","family":"Nebel","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"ref_1","first-page":"312","article-title":"Genetic influence on human lifespan and longevity","volume":"119","author":"Hjelmborg","year":"2006","journal-title":"Qual. 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