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

Nature Communications

Volumn 8, Issue 1, 2017, Pages

  Joshi, Peter K ^a   Pirastu, Nicola ^a   Kentistou, Katherine A ^a,b   Fischer, Krista ^c   Hofer, Edith ^d   Schraut, Katharina E ^a,b   Clark, David W ^a   Nutile, Teresa ^e   Barnes, Catriona L K ^a   Timmers, Paul R H J ^a   Shen, Xia ^a,f   Gandin, Ilaria ^g,h   McDaid, Aaron F ^i,j   Hansen, Thomas Folkmann ^k,l   Gordon, Scott D ^m   Giulianini, Franco ⁿ   Boutin, Thibaud S ^o   Abdellaoui, Abdel ^p   Zhao, Wei ^q   Medina Gomez, Carolina ^r   Bartz, Traci M ^s   Trompet, Stella ^t   Lange, Leslie A ^u   Raffield, Laura ^v   Van Der Spek, Ashley ^r   Galesloot, Tessel E ^w   Proitsi, Petroula ^x   Yanek, Lisa R ^y   Bielak, Lawrence F ^q   Payton, Antony ^z   Murgia, Federico ^aa,ap   Concas, Maria Pina ^ab   Biino, Ginevra ^ac   Tajuddin, Salman M ^ad   Seppälä, Ilkka ^ae   Amin, Najaf ^r   Boerwinkle, Eric ^af   Børglum, Anders D ^l,ag   Campbell, Archie ^ah   Demerath, Ellen W ^ai   Demuth, Ilja ^aj   Faul, Jessica D ^q   Ford, Ian ^ak   Gialluisi, Alessandro ^al   Gögele, Martin ^aa,ap   Graff, Mariaelisa ^am   Hingorani, Aroon ^x   Hottenga, Jouke Jan ^p   Hougaard, David M ^l,an   Hurme, Mikko A ^ae   Ikram, M Arfan ^r   Jylhä, Marja ^ao   Kuh, Diana ^x   Ligthart, Lannie ^p   Lill, Christina M ^ap   Lindenberger, Ulman ^aq,ar   Lumley, Thomas ^as   Mägi, Reedik ^c   Marques Vidal, Pedro ^at   Medland, Sarah E ^m   Milani, Lili ^c   Nagy, Reka ^o   Ollier, William E R ^z   Peyser, Patricia A ^q   Pramstaller, Peter P ^aa,ap   Ridker, Paul M ^n,au   Rivadeneira, Fernando ^r   Ruggiero, Daniela ^e   Saba, Yasaman ^d   Schmidt, Reinhold ^d   Schmidt, Helena ^d   Slagboom, P Eline ^t   Smith, Blair H ^av   Smith, Jennifer A ^q   Sotoodehnia, Nona ^s   Steinhagen Thiessen, Elisabeth ^aj   Van Rooij, Frank J A ^r   Verbeek, André L ^w   Vermeulen, Sita H ^w   Vollenweider, Peter ^at   Wang, Yunpeng ^l,aw   Werge, Thomas ^k,l   Whitfield, John B ^m   Zonderman, Alan B ^ad   Lehtimäki, Terho ^ae   Evans, Michele K ^ad   Pirastu, Mario ^ab   Fuchsberger, Christian ^aa,ap   Bertram, Lars ^ap,ax   Pendleton, Neil ^z   Kardia, Sharon L R ^q   Ciullo, Marina ^e,al   Becker, Diane M ^y   Wong, Andrew ^x   Psaty, Bruce M ^s,ay   Van Duijn, Cornelia M ^r   Wilson, James G ^az   Jukema, J Wouter ^t   Kiemeney, Lambertus ^w   Uitterlinden, André G ^r   Franceschini, Nora ^am   North, Kari E ^am   Weir, David R ^q   Metspalu, Andres ^c   Boomsma, Dorret I ^p   Hayward, Caroline ^o   Chasman, Daniel ^n,au   Martin, Nicholas G ^m   Sattar, Naveed ^ba   Campbell, Harry ^a   Esko, Tonu ^c,bb   Kutalik, Zoltán ^i,j   Wilson, James F ^a,o   more..

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

^c UNIVERSITY OF TARTU   (Estonia)

^d MEDICAL UNIVERSITY OF GRAZ   (Austria)

^e INSTITUTE OF GENETICS AND BIOPHYSICS ADRIANO BUZZATI TRAVERSO   (Italy)

^f KAROLINSKA INSTITUTE   (Sweden)

^g UNIVERSITY OF TRIESTE   (Italy)

^h INSTITUTE FOR MATERNAL AND CHILD HEALTH IRCCS BURLO GAROFOLO   (Italy)

ⁱ UNIVERSITY OF LAUSANNE   (Switzerland)

^j SWISS INSTITUTE OF BIOINFORMATICS   (Switzerland)

^k Mental Health Centre St Hans   (Denmark)

^l Lundbeck Foundation Initiative for Integrative Psychiatric Research   (Denmark)

^m QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

ⁿ BRIGHAM AND WOMEN S HOSPITAL   (United States)

^o UNIVERSITY OF EDINBURGH   (United Kingdom)

^p UNIVERSITY OF AMSTERDAM   (Netherlands)

^q UNIVERSITY OF MICHIGAN   (United States)

^r ERASMUS MEDICAL CENTER   (Netherlands)

^s UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^t LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^u UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^v UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^w RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^x UNIVERSITY COLLEGE LONDON   (United Kingdom)

^y JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^z UNIVERSITY OF MANCHESTER   (United Kingdom)

^aa University of Lubeck   (Italy)

^ab Milan Unit   (Italy)

^ac CNR   (Italy)

^ad NATIONAL INSTITUTE ON AGING   (United States)

^ae TAMPERE UNIVERSITY OF TECHNOLOGY   (Finland)

^af UNIVERSITY OF TEXAS SCHOOL OF PUBLIC HEALTH   (United States)

^ag AARHUS UNIVERSITY   (Denmark)

^ah UNIVERSITY OF EDINBURGH   (United Kingdom)

^ai UNIVERSITY OF MINNESOTA   (United States)

^aj CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^ak UNIVERSITY OF GLASGOW   (United Kingdom)

^al IRCCS NEUROMED   (Italy)

^am University of North Carolina at Chapel Hill   (United States)

^an STATENS SERUM INSTITUT   (Denmark)

^ao Jyvaskyla University   (Finland)

^ap UNIVERSITY OF LÜBECK   (Germany)

^aq MAX PLANCK INSTITUTE FOR HUMAN DEVELOPMENT   (Germany)

^ar MAX PLANCK UCL CENTRE FOR COMPUTATIONAL PSYCHIATRY AND AGEING RESEARCH   (United Kingdom)

^as UNIVERSITY OF AUCKLAND   (New Zealand)

^at LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^au HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^av UNIVERSITY OF DUNDEE   (United Kingdom)

^aw UNIVERSITY OF OSLO   (Norway)

^ax IMPERIAL COLLEGE LONDON   (United Kingdom)

^ay KAISER PERMANENTE   (United States)

^az UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

^ba UNIVERSITY OF GLASGOW   (United Kingdom)

^bb BROAD INSTITUTE OF MIT AND HARVARD   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN E; C REACTIVE PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 2A; CYCLIN DEPENDENT KINASE INHIBITOR 2B; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HLA DQA1 ANTIGEN; HLA DRB1 ANTIGEN; INSULIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NICOTINIC RECEPTOR; OMEGA 3 FATTY ACID; TRANSCRIPTION FACTOR FKHRL1; TRIACYLGLYCEROL; HIGH DENSITY LIPOPROTEIN; HLA DQ ANTIGEN; HLA-DQA1 ANTIGEN; LIPOPROTEIN A;

BODY MASS; GENOME; GENOMICS; LONGEVITY; META-ANALYSIS; OBESITY; PROTEOMICS; SMOKING;

ADULT; AGED; ALZHEIMER DISEASE; ARTICLE; BLOOD PRESSURE; BODY FAT; BODY MASS; BRAIN ISCHEMIA; BREAST CANCER; CAUSALITY; CHEMICAL STRUCTURE; CHOLESTEROL BLOOD LEVEL; CORONARY ARTERY DISEASE; DIET RESTRICTION; DISEASE PREDISPOSITION; EDUCATIONAL STATUS; EXPERIENCE; FEMALE; GENE LOCUS; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENOME-WIDE ASSOCIATION STUDY; HUMAN; INSULIN RESISTANCE; LIFESPAN; LIFESTYLE; LONGEVITY; LUNG CANCER; MAJOR CLINICAL STUDY; MALE; MENARCHE; MENDELIAN RANDOMIZATION ANALYSIS; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PARENT; PHENOTYPE; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; SMOKING; SOCIAL STATUS; SQUAMOUS CELL LUNG CARCINOMA; SURVIVAL; WAIST HIP RATIO; ALLELE; BLOOD; COMPLICATION; EDUCATION; GENETIC PREDISPOSITION; GENETICS; LUNG TUMOR; META ANALYSIS; SOCIOECONOMICS;

ALLELES; BODY MASS INDEX; CORONARY DISEASE; EDUCATION; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HLA-DQ ALPHA-CHAINS; HLA-DRB1 CHAINS; HUMANS; INSULIN RESISTANCE; LIFE STYLE; LIPOPROTEIN(A); LIPOPROTEINS, HDL; LONGEVITY; LUNG NEOPLASMS; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE; SMOKING; SOCIOECONOMIC FACTORS;

EID: 85031691125     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-017-00934-5     Document Type: Article

References (53)

1. Herskind, A. M. et al. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. Hum. Genet. 97, 319-323 (1996).
2. Deelen, J. et al. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell 10, 686-698 (2011).
3. Broer, L. et al. GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy. J. Gerontol. A Biol. Sci. Med. Sci. 70, 110-118 (2015).
4. Joshi, P. K. et al. Variants near CHRNA3/5 and APOE have age-and sexrelated effects on human lifespan. Nat. Commun. 7, 11174 (2016).
5. Pilling, L. C. et al. Human longevity is influenced by many genetic variants: evidence from 75, 000 UK Biobank participants. Aging 8, 547-560 (2016).
6. Deelen, J. et al. Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age. Hum. Mol. Genet. 23, 4420-4432 (2014).
7. Wacholder, S. et al. The kin-cohort study for estimating penetrance. Am. J. Epidemiol. 148, 623-630 (1998).
8. Staley, J. R. et al. PhenoScanner: a database of human genotype-phenotype associations. Bioinformatics 32, 3207-3209 (2016).
9. Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236-1241 (2015).
10. Hemani, G. et al. MR-Base: a platform for systematic causal inference across the phenome using billions of genetic associations. bioRxiv doi: https://doi. org/10. 1101/078972 (2016).
11. Michailidou, K. et al. Genome-wide association analysis of more than 120, 000 individuals identifies 15 new susceptibility loci for breast cancer. Nat. Genet. 47, 373-380 (2015).
12. Dehghan, A. et al. Meta-analysis of genome-wide association studies in > 80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation 123, 731-738 (2011).
13. Utermann, G. et al. Lp (a) glycoprotein phenotypes. Inheritance and relation to Lp (a)-lipoprotein concentrations in plasma. J. Clin. Invest. 80, 458 (1987).
14. Schmidt, K., Noureen, A., Kronenberg, F. & Utermann, G. Structure, function, and genetics of lipoprotein (a). J. Lipid Res. 57, 1339-1359 (2016).
15. Kamstrup, P. R. & Nordestgaard, B. G. Lipoprotein (a) concentrations, isoform size, and risk of type 2 diabetes: a Mendelian randomisation study. Lancet Diabetes Endocrinol. 1, 220-227 (2013).
16. Mora, S. et al. Lipoprotein (a) and risk of type 2 diabetes. Clin. Chem. 56, 1252-1260 (2010).
17. Clarke, R. et al. Genetic variants associated with Lp (a) lipoprotein level and coronary disease. New Engl. J. Med. 361, 2518-2528 (2009).
18. Stuart, P. E. et al. Genome-wide association analysis of psoriatic arthritis and cutaneous psoriasis reveals differences in their genetic architecture. Am. J. Hum. Genet. 97, 816-836 (2015).
19. Okada, Y. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376-381 (2014).
20. De Jager, P. L. et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat. Genet. 41, 776-782 (2009).
21. Burton, P. R. et al. Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 447, 661-678 (2007).
22. Fortney, K. et al. Genome-wide scan informed by age-related disease identifies loci for exceptional human longevity. PLoS Genet. 11, e1005728 (2015).
23. Willcox, B. J. et al. FOXO3A genotype is strongly associated with human longevity. Proc. Natl Acad. Sci. 105, 13987-13992 (2008).
24. Consortium, C. A. D. G. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat. Genet. 43, 339-344 (2011).
25. Barrett, J. C. et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41, 703-707 (2009).
26. Ehret, G. B. et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103-109 (2011).
27. Eriksson, N. et al. Novel associations for hypothyroidism include known autoimmune risk loci. PLoS ONE 7, e34442 (2012).
28. Liu, J. Z. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat. Genet. 47, 979-986 (2015).
29. Gudbjartsson, D. F. et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat. Genet. 41, 342-347 (2009).
30. Reininghaus, U. et al. Mortality in schizophrenia and other psychoses: a 10-year follow-up of the SOP first-episode cohort. Schizophr. Bull. 41, 664-673 (2015).
31. Stevens, P. E. & Levin, A., Kidney disease: improving global outcomes chronic kidney disease guideline development work group, Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann. Intern. Med. 158, 825-830 (2013).
32. Martin-Maria, N. et al. The impact of subjective well-being on mortality: a meta-analysis of longitudinal studies in the general population. Psychosom. Med. 79, 565-575 (2017).
33. Jia, H., Zack, M. M., Thompson, W. W., Crosby, A. E. & Gottesman, I. I. Impact of depression on quality-adjusted life expectancy (QALE) directly as well as indirectly through suicide. Soc. Psychiatry Psychiatr. Epidemiol. 50, 939-949 (2015).
34. Benziger, C. P., Roth, G. A. & Moran, A. E. The global burden of disease study and the preventable burden of NCD. Glob. Heart 11, 393-397 (2016).
35. Zimmermann, O. et al. C-reactive protein in human atherogenesis: facts and fiction. Mediators Inflamm. 2014, 561428 (2014).
36. Natriuretic Peptides Studies, C. et al. Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data metaanalysis. Lancet Diabetes Endocrinol. 4, 840-849 (2016).
37. Global, B. M. I. M. C. et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 388, 776-786 (2016).
38. Cox, D. R. Regression models and life-tables. J. R. Stat. Soc. Ser. B Stat. Methodol. 34, 187 (1972).
39. Therneau, T. M., Grambsch, P. M. & Fleming, T. R. Martingale-based residuals for survival models. Biometrika 77, 147-160 (1990).
40. Haller, T., Kals, M., Esko, T., Magi, R. & Fischer, K. RegScan: a GWAS tool for quick estimation of allele effects on continuous traits and their combinations. Brief Bioinform. 16, 39-44 (2015).
41. Winkler, T. W. et al. Quality control and conduct of genome-wide association meta-analyses. Nat. Protoc. 9, 1192-1212 (2014).
42. Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190-2191 (2010).
43. Machiela, M. J. & Chanock, S. J. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics 31, 3555-3557 (2015).
44. Emanuele, E., Fontana, J. M., Minoretti, P. & Geroldi, D. Preliminary evidence of a genetic association between chromosome 9p21. 3 and human longevity. Rejuvenation Res. 13, 23-26 (2010).
45. Flachsbart, F. et al. Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc. Natl Acad. Sci. 106, 2700-2705 (2009).
46. Malovini, A. et al. Association study on long-living individuals from Southern Italy identifies rs10491334 in the CAMKIV gene that regulates survival proteins. Rejuvenation Res. 14, 283-291 (2011).
47. Newman, A. B. et al. A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the cohorts for heart and aging research in genomic epidemiology consortium. J. Gerontol. A Biol. Sci. Med. Sci. 65, 478-487 (2010).
48. Zeng, Y. et al. Novel loci and pathways significantly associated with longevity. Sci. Rep. 6, 21243 (2016).
49. Zheng, J. et al. LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics 33, 272-279 (2017).
50. Ehret, G. B. et al. The genetics of blood pressure regulation and its target organs from association studies in 342, 415 individuals. Nat. Genet. 48, 1171-1184 (2016).
51. Revelle, W. Hierarchical cluster analysis and the internal structure of tests. Multivariate Behav. Res. 14, 57-74 (1979).
52. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575 (2007).
53. Sudlow, C. et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015).