Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

Joshi, P. K. et al. (2017) Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nature Communications, 8(1), 910. (doi: 10.1038/s41467-017-00934-5) (PMID:29030599) (PMCID:PMC5715013)

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Abstract

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ford, Professor Ian and Sattar, Professor Naveed
Authors: Joshi, P. K., Pirastu, N., Kentistou, K. A., Fischer, K., Hofer, E., Schraut, K. E., Clark, D. W., Nutile, T., Barnes, C. L. K., Timmers, P. R. H. J., Shen, X., Gandin, I., McDaid, A. F., Hansen, T. F., Gordon, S. D., Giulianini, F., Boutin, T. S., Abdellaoui, A., Zhao, W., Medina-Gomez, C., Bartz, T. M., Trompet, S., Lange, L. A., Raffield, L., van der Spek, A., Galesloot, T. E., Proitsi, P., Yanek, L. R., Bielak, L. F., Payton, A., Murgia, F., Concas, M. P., Biino, G., Tajuddin, S. M., Seppälä, I., Amin, N., Boerwinkle, E., Børglum, A. D., Campbell, A., Demerath, E. W., Demuth, I., Faul, J. D., Ford, I., Gialluisi, A., Gögele, M., Graff, M., Hingorani, A., Hottenga, J.-J., Hougaard, D. M., Hurme, M. A., Ikram, M. A., Jylhä, M., Kuh, D., Ligthart, L., Lill, C. M., Lindenberger, U., Lumley, T., Mägi, R., Marques-Vidal, P., Medland, S. E., Milani, L., Nagy, R., Ollier, W. E. R., Peyser, P. A., Pramstaller, P. P., Ridker, P. M., Rivadeneira, F., Ruggiero, D., Saba, Y., Schmidt, R., Schmidt, H., Slagboom, P. E., Smith, B. H., Smith, J. A., Sotoodehnia, N., Steinhagen-Thiessen, E., van Rooij, F. J. A., Verbeek, A. L., Vermeulen, S. H., Vollenweider, P., Wang, Y., Werge, T., Whitfield, J. B., Zonderman, A. B., Lehtimäki, T., Evans, M. K., Pirastu, M., Fuchsberger, C., Bertram, L., Pendleton, N., Kardia, S. L. R., Ciullo, M., Becker, D. M., Wong, A., Psaty, B. M., van Duijn, C. M., Wilson, J. G., Jukema, J. W., Kiemeney, L., Uitterlinden, A. G., Franceschini, N., North, K. E., Weir, D. R., Metspalu, A., Boomsma, D. I., Hayward, C., Chasman, D., Martin, N. G., Sattar, N., Campbell, H., Esko, T., Kutalik, Z., and Wilson, J. F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Nature Communications 8(1):910
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS