Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances.

TitreGenomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances.
Publication TypeJournal Article
Year of Publication2019
AuthorsTimmers, PRhj, Mounier, N, Lall, K, Fischer, K, Ning, Z, Feng, X, Bretherick, AD, Clark, DW, Agbessi, M, Ahsan, H, Alves, I, Andiappan, A, Awadalla, P, Battle, A, Bonder, MJ, Boomsma, D, Christiansen, M, Claringbould, A, Deelen, P, van Dongen, J, Esko, T, Favé, M, Franke, L, Frayling, T, Gharib, SA, Gibson, G, Hemani, G, Jansen, R, Kalnapenkis, A, Kasela, S, Kettunen, J, Kim, Y, Kirsten, H, Kovacs, P, Krohn, K, Kronberg-Guzman, J, Kukushkina, V, Kutalik, Z, Kähönen, M, Lee, B, Lehtimäki, T, Loeffler, M, Marigorta, U, Metspalu, A, van Meurs, J, Milani, L, Müller-Nurasyid, M, Nauck, M, Nivard, M, Penninx, B, Perola, M, Pervjakova, N, Pierce, B, Powell, J, Prokisch, H, Psaty, BM, Raitakari, O, Ring, S, Ripatti, S, Rotzschke, O, Rüeger, S, Saha, A, Scholz, M, Schramm, K, Seppälä, I, Stumvoll, M, Sullivan, P, Teumer, A, Thiery, J, Tong, L, Tönjes, A, Verlouw, J, Visscher, PM, Võsa, U, Völker, U, Yaghootkar, H, Yang, J, Zeng, B, Zhang, F, Agbessi, M, Ahsan, H, Alves, I, Andiappan, A, Awadalla, P, Battle, A, Bonder, MJ, Boomsma, D, Christiansen, M, Claringbould, A, Deelen, P, van Dongen, J, Esko, T, Favé, M, Franke, L, Frayling, T, Gharib, SA, Gibson, G, Hemani, G, Jansen, R, Kalnapenkis, A, Kasela, S, Kettunen, J, Kim, Y, Kirsten, H, Kovacs, P, Krohn, K, Kronberg-Guzman, J, Kukushkina, V, Kutalik, Z, Kähönen, M, Lee, B, Lehtimäki, T, Loeffler, M, Marigorta, U, Metspalu, A, van Meurs, J, Milani, L, Müller-Nurasyid, M, Nauck, M, Nivard, M, Penninx, B, Perola, M, Pervjakova, N, Pierce, B, Powell, J, Prokisch, H, Psaty, BM, Raitakari, O, Ring, S, Ripatti, S, Rotzschke, O, Rüeger, S, Saha, A, Scholz, M, Schramm, K, Seppälä, I, Stumvoll, M, Sullivan, P, Teumer, A, Thiery, J, Tong, L, Tönjes, A, Verlouw, J, Visscher, PM, Võsa, U, Völker, U, Yaghootkar, H, Yang, J, Zeng, B, Zhang, F, Shen, X, Esko, T, Kutalik, Z, Wilson, JF, Joshi, PK
Corporate AuthorseQTLGen Consortium
JournalElife
Volume8
Date Published01/2019
DOI10.7554/eLife.39856
ISSN2050-084X
Mots-cléscomplex trait, genetics, Genomics, human, lifespan, Longevity
Abstract

We use a genome-wide association of 1 million parental lifespans of genotyped subjects and data on mortality risk factors to validate previously unreplicated findings near , , , , , and 13q21.31, and identify and replicate novel findings near , , and . We also validate previous findings near 5q33.3/ and , whilst finding contradictory evidence at other loci. Gene set and cell-specific analyses show that expression in foetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are gene pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Individual genetic variants that increase dementia, cardiovascular disease, and lung cancer - but not other cancers - explain the most variance. Resulting polygenic scores show a mean lifespan difference of around five years of life across the deciles.

Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Alternate URL

http://www.ncbi.nlm.nih.gov/pubmed/30642433?dopt=Abstract

WOS ID (UT)

000455564600001

Alternate JournalElife
Citation Key / SERVAL ID9394
Peer reviewRefereed
PubMed ID30642433
PubMed Central IDPMC6333444
Grant ListDTP in Precision Medicine MR/N013166/1,HGU QTL in health and disease / / Medical Research Council / United Kingdom
PUT 1665 / / Estonian Research Competency Council /
PhD Training Fellowship for Clinicians / / Wellcome Trust / United Kingdom
204979/Z/16/Z / / Edinburgh Clinical Academic Track /
2014-00371 / / Svenska Forskningsrådet Formas /
2017-02543 / / Svenska Forskningsrådet Formas /
31003A_169929 / / Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung /
51RTP0_151019 / / SystemsX.ch /
                         

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