Sökning: onr:"swepub:oai:DiVA.org:uu-223056" > Genetic determinant...
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000 | 03535naa a2200385 4500 | |
001 | oai:DiVA.org:uu-223056 | |
003 | SwePub | |
008 | 140416s2013 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:126598777 | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2230562 URI |
024 | 7 | a https://doi.org/10.1007/s00439-013-1267-62 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1265987772 URI |
040 | a (SwePub)uud (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Ganna, Andrea,d 1985-u Karolinska Institutet4 aut |
245 | 1 0 | a Genetic determinants of mortality :b Can findings from genome-wide association studies explain variation in human mortality? |
264 | c 2013-01-25 | |
264 | 1 | b Springer Science and Business Media LLC,c 2013 |
338 | a print2 rdacarrier | |
520 | a Twin studies have estimated the heritability of longevity to be approximately 20-30 %. Genome-wide association studies (GWAS) have revealed a large number of determinants of morbidity, but so far, no new polymorphisms have been discovered to be associated with longevity per se in GWAS. We aim to determine whether the genetic architecture of mortality can be explained by single nucleotide polymorphisms (SNPs) associated with common traits and diseases related to mortality. By extensive quality control of published GWAS we created a genetic score from 707 common SNPs associated with 125 diseases or risk factors related with overall mortality. We prospectively studied the association of the genetic score with: (1) time-to-death; (2) incidence of the first of nine major diseases (coronary heart disease, stroke, heart failure, diabetes, dementia, lung, breast, colon and prostate cancers) in two population-based cohorts of Dutch and Swedish individuals (N = 15,039; age range 47-99 years). During a median follow-up of 6.3 years (max 22.2 years), we observed 4,318 deaths and 2,132 incident disease events. The genetic score was significantly associated with time-to-death [hazard ratio (HR) per added risk allele = 1.003, P value = 0.006; HR 4th vs. 1st quartile = 1.103]. The association between the genetic score and incidence of major diseases was stronger (HR per added risk allele = 1.004, P value = 0.002; HR 4th vs. 1st quartile = 1.160). Associations were stronger for individuals dying at older ages. Our findings are compatible with the view of mortality as a complex and highly polygenetic trait, not easily explainable by common genetic variants related to diseases and physiological traits. | |
700 | 1 | a Rivadeneira, Fernando4 aut |
700 | 1 | a Hofman, Albert4 aut |
700 | 1 | a Uitterlinden, André G4 aut |
700 | 1 | a Magnusson, Patrik K Eu Karolinska Institutet4 aut |
700 | 1 | a Pedersen, Nancy Lu Karolinska Institutet4 aut |
700 | 1 | a Ingelsson, Erik,d 1975-u Department of Medical Epidemiology and Biostatistics, Karolinska Institutet4 aut0 (Swepub:uu)ering425 |
700 | 1 | a Tiemeier, Henning4 aut |
710 | 2 | a Karolinska Institutetb Department of Medical Epidemiology and Biostatistics, Karolinska Institutet4 org |
773 | 0 | t Human Geneticsd : Springer Science and Business Media LLCg 132:5, s. 553-561q 132:5<553-561x 0340-6717x 1432-1203 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-223056 |
856 | 4 8 | u https://doi.org/10.1007/s00439-013-1267-6 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:126598777 |
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