@article {7981, title = {Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Jan 15}, 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{\textquoteright}s assessment is that all the issues have been addressed (see decision letter).

}, issn = {2050-084X}, doi = {10.7554/eLife.39856}, author = {Timmers, Paul Rhj and Mounier, Ninon and L{\"a}ll, Kristi and Fischer, Krista and Ning, Zheng and Feng, Xiao and Bretherick, Andrew D and Clark, David W and Agbessi, M and Ahsan, H and Alves, I and Andiappan, A and Awadalla, P and Battle, A and Bonder, M J and Boomsma, D and Christiansen, M and Claringbould, A and Deelen, P and van Dongen, J and Esko, T and Fav{\'e}, M and Franke, L and Frayling, T and Gharib, S A and Gibson, G and Hemani, G and Jansen, R and Kalnapenkis, A and Kasela, S and Kettunen, J and Kim, Y and Kirsten, H and Kovacs, P and Krohn, K and Kronberg-Guzman, J and Kukushkina, V and Kutalik, Z and K{\"a}h{\"o}nen, M and Lee, B and Lehtim{\"a}ki, T and Loeffler, M and Marigorta, U and Metspalu, A and van Meurs, J and Milani, L and M{\"u}ller-Nurasyid, M and Nauck, M and Nivard, M and Penninx, B and Perola, M and Pervjakova, N and Pierce, B and Powell, J and Prokisch, H and Psaty, B M and Raitakari, O and Ring, S and Ripatti, S and Rotzschke, O and Ru{\"e}ger, S and Saha, A and Scholz, M and Schramm, K and Sepp{\"a}l{\"a}, I and Stumvoll, M and Sullivan, P and Teumer, A and Thiery, J and Tong, L and T{\"o}njes, A and Verlouw, J and Visscher, P M and V{\~o}sa, U and V{\"o}lker, U and Yaghootkar, H and Yang, J and Zeng, B and Zhang, F and Agbessi, M and Ahsan, H and Alves, I and Andiappan, A and Awadalla, P and Battle, A and Bonder, M J and Boomsma, D and Christiansen, M and Claringbould, A and Deelen, P and van Dongen, J and Esko, T and Fav{\'e}, M and Franke, L and Frayling, T and Gharib, S A and Gibson, G and Hemani, G and Jansen, R and Kalnapenkis, A and Kasela, S and Kettunen, J and Kim, Y and Kirsten, H and Kovacs, P and Krohn, K and Kronberg-Guzman, J and Kukushkina, V and Kutalik, Z and K{\"a}h{\"o}nen, M and Lee, B and Lehtim{\"a}ki, T and Loeffler, M and Marigorta, U and Metspalu, A and van Meurs, J and Milani, L and M{\"u}ller-Nurasyid, M and Nauck, M and Nivard, M and Penninx, B and Perola, M and Pervjakova, N and Pierce, B and Powell, J and Prokisch, H and Psaty, B M and Raitakari, O and Ring, S and Ripatti, S and Rotzschke, O and Ru{\"e}ger, S and Saha, A and Scholz, M and Schramm, K and Sepp{\"a}l{\"a}, I and Stumvoll, M and Sullivan, P and Teumer, A and Thiery, J and Tong, L and T{\"o}njes, A and Verlouw, J and Visscher, P M and V{\~o}sa, U and V{\"o}lker, U and Yaghootkar, H and Yang, J and Zeng, B and Zhang, F and Shen, Xia and Esko, T{\~o}nu and Kutalik, Zolt{\'a}n and Wilson, James F and Joshi, Peter K} }