دورية أكاديمية
Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age.
| العنوان: | Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age. |
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| المؤلفون: | Deelen, Joris, Beekman, Marian, Uh, Hae-Won, Broer, Linda, Ayers, Kristin L, Tan, Qihua, Kamatani, Yoichiro, Bennet, Anna M, Tamm, Riin, Trompet, Stella, Guðbjartsson, Daníel F, Flachsbart, Friederike, Rose, Giuseppina, Viktorin, Alexander, Fischer, Krista, Nygaard, Marianne, Cordell, Heather J, Crocco, Paolina, van den Akker, Erik B, Böhringer, Stefan, Helmer, Quinta, Nelson, Christopher P, Saunders, Gary I, Alver, Maris, Andersen-Ranberg, Karen, Breen, Marie E, van der Breggen, Ruud, Caliebe, Amke, Capri, Miriam, Cevenini, Elisa, Collerton, Joanna C, Dato, Serena, Davies, Karen, Ford, Ian, Gampe, Jutta, Garagnani, Paolo, de Geus, Eco J C, Harrow, Jennifer, van Heemst, Diana, Heijmans, Bastiaan T, Heinsen, Femke-Anouska, Hottenga, Jouke-Jan, Hofman, Albert, Jeune, Bernard, Jonsson, Palmi V, Lathrop, Mark, Lechner, Doris, Martin-Ruiz, Carmen, Mcnerlan, Susan E, Mihailov, Evelin, Montesanto, Alberto, Mooijaart, Simon P, Murphy, Anne, Nohr, Ellen A, Paternoster, Lavinia, Postmus, Iris, Rivadeneira, Fernando, Ross, Owen A, Salvioli, Stefano, Sattar, Naveed, Schreiber, Stefan, Stefánsson, Hreinn, Stott, David J, Tiemeier, Henning, Uitterlinden, André G, Westendorp, Rudi G J, Willemsen, Gonneke, Samani, Nilesh J, Galan, Pilar, Sørensen, Thorkild I A, Boomsma, Dorret I, Jukema, J Wouter, Rea, Irene Maeve, Passarino, Giuseppe, de Craen, Anton J M, Christensen, Kaare, Nebel, Almut, Stefánsson, Kári, Metspalu, Andres, Magnusson, Patrik, Blanché, Hélène, Christiansen, Lene, Kirkwood, Thomas B L, van Duijn, Cornelia M, Franceschi, Claudio, Houwing-Duistermaat, Jeanine J, Slagboom, P Eline |
| المساهمون: | Leiden Univ, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands 2 Leiden Univ, Netherlands Consortium Healthy Ageing, NL-2300 RC Leiden, Netherlands 3 Leiden Univ, Dept Med Stat & Bioinformat, NL-2300 RC Leiden, Netherlands 4 Leiden Univ, Dept Cardiol, NL-2300 RC Leiden, Netherlands 5 Leiden Univ, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands 6 Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands 7 Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands 8 Newcastle Univ, Int Ctr Life, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England 9 Univ So Denmark, Inst Publ Hlth, DK-5000 Odense C, Denmark 10 Univ So Denmark, Inst Clin Res, Dept Gynecol & Obstet, DK-5000 Odense C, Denmark 11 Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark 12 Odense Univ Hosp, Clin Biochem & Pharmacol, DK-5000 Odense C, Denmark 13 Fdn Jean Dausset CEPH, F-75010 Paris, France 14 Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden 15 Univ Tartu, Estonian Genome Ctr, Tartu 51010, Estonia 16 Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia 17 deCODE Genet, Populat Gen, IS-101 Reykjavik, Iceland 18 Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany 19 Univ Kiel, Inst Med Informat & Stat, D-24105 Kiel, Germany 20 Univ Calabria, Dept Biol Ecol & Earth Sci, I-87036 Arcavacata Di Rende, Italy 21 Delft Univ Technol, Delft Bioinformat Lab, NL-2600 GA Delft, Netherlands 22 Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England 23 Glenfield Hosp, Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester LE3 9QP, Leics, England 24 Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England 25 Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast BT9 7BL, Antrim, North Ireland 26 Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA 27 Univ Bologna, Dept Expt Diagnost & Specialty Med, I-40126 Bologna, Italy 28 Univ Bologna, Interdepartmental Ctr L Galvani, I-40126 Bologna, Italy 29 Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England 30 Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland 31 Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland 32 Max Planck Inst Demograf Forsch, Lab Stat Demog, D-18057 Rostock, Germany 33 Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands 34 Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands 35 Landspitali Univ Hosp, IS-101 Reykjavik, Iceland 36 Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland 37 CEA, Inst Genom, F-91057 Evry, France 38 McGill Univ, Montreal, PQ H3G 1A4, Canada 39 Genome Quebec Innovat Ctr, Montreal, PQ H3G 1A4, Canada 40 Belfast Hlth & Social Care Trust, Cytogenet Lab, Belfast BT8 8BH, Antrim, North Ireland 41 Estonian Bioctr, EE-51010 Tartu, Estonia 42 Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, DK-8000 Aarhus C, Denmark 43 Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England 44 Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA 45 Univ Glasgow, Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland 46 Univ Kiel, PopGen Biobank, D-24105 Kiel, Germany 47 Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany 48 Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CA Rotterdam, Netherlands 49 Univ Paris 04, UREN, U557, INSERM, F-93017 Bobigny, France 50 U1125 Inra, F-93017 Bobigny, France 51 Cnam, F-93017 Bobigny, France 52 Univ Paris 13, CRNH IdF, F-93017 Bobigny, France 53 Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr, DK-2200 Copenhagen N, Denmark 54 Inst Prevent Med, DK-2000 Copenhagen, Denmark 55 Frederiksberg Univ Hosp, DK-2000 Copenhagen, Denmark 56 Interuniv Cardiol Inst Netherlands, NL-3501 DG Utrecht, Netherlands 57 Bellaria Hosp, IRCCS Inst Neurol Sci, I-40139 Bologna, Italy 58 CNR, ISOF, I-40129 Bologna, Italy |
| بيانات النشر: | Oxford Univ Press |
| سنة النشر: | 2014 |
| المجموعة: | Hirsla - Landspítali University Hospital research archive |
| مصطلحات موضوعية: | Lífslíkur, Öldrun, Arfgengi, Aged, 80 and over, Longevity/genetics, Genome-Wide Association Study, Genome, Human, Genetic Loci, Genetic Linkage, Europe, Aging/genetics, Disease/genetics |
| الوصف: | To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. ; The genetic contribution to the variation in human lifespan is ∼ 25%. Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality. We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16 121 younger controls (<65 years) followed by replication in an additional set of 13 060 long-lived individuals and 61 156 controls. In addition, we performed a subset analysis in cases aged ≥ 90 years. We observed genome-wide significant association with longevity, as reflected by survival to ages beyond 90 years, at a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P = 1.74 × 10(-8)). We also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P = 3.40 × 10(-36)), representing the TOMM40/APOE/APOC1 locus. In a prospective meta-analysis (n = 34 103), the minor allele of rs2149954 (T) on chromosome 5q33.3 associates with increased survival (HR = 0.95, P = 0.003). This allele has previously been reported to associate with low blood pressure in middle age. Interestingly, the minor allele (T) associates with decreased cardiovascular mortality risk, independent of blood pressure. We report on the first GWAS-identified longevity locus on chromosome 5q33.3 influencing survival in the general European population. The minor allele of this locus associates with low blood pressure in middle age, although the contribution of this allele to survival may be less dependent on blood pressure. Hence, the pleiotropic mechanisms by which this intragenic variation contributes to lifespan regulation have to be elucidated. ; Augustinus Foundation Avera Institute for Human Genetics (AIHG) AXA Research Fund Belfast City Hospital Trust Fund Biobanking and Biomolecular Resources Research ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1460-2083 |
| العلاقة: | info:eu-repo/grantAgreement/EC/FP7/201413; info:eu-repo/grantAgreement/EC/FP7/202047; info:eu-repo/grantAgreement/EC/FP7/242244; info:eu-repo/grantAgreement/EC/FP7/259679; http://dx.doi.org/10.1093/hmg/ddu139Test; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103672Test/; Hum. Mol. Genet. 2014, 23 (16):4420-32; http://hdl.handle.net/2336/325825Test; Human molecular genetics |
| DOI: | 10.1093/hmg/ddu139 |
| الإتاحة: | https://doi.org/10.1093/hmg/ddu139Test http://hdl.handle.net/2336/325825Test |
| حقوق: | openAccess ; Open Access |
| رقم الانضمام: | edsbas.AB31F6A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14602083 |
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| DOI: | 10.1093/hmg/ddu139 |