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LIBRIS Formathandbok  (Information om MARC21)
00006040naa a2200925 4500
008160815s2016 | |||||||||||000 ||eng|
024a urn:nbn:se:umu:diva-1245122 urn
024a https://doi.org/10.1001/jamaneurol.2016.11142 DOI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Fogh, Isabella4 aut
2451 0a Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis
264 1c 2016
338 a print2 rdacarrier
520 a IMPORTANCE Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset. OBJECTIVE To identify gene variants influencing survival in ALS. DESIGN, SETTING, AND PARTICIPANTS This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015. MAIN OUTCOMES AND MEASURES Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed bymeta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis. RESULTS Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 x 10(-9)) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 x 10(-8)). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 x 10(-9)), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208 CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 x 10(-8)), corresponding to a 4-month reduction in survival compared with TT carriers. CONCLUSIONS AND RELEVANCE This GWAS robustly identified 2 loci at genome-wide levels of significance that influence survival in patients with ALS. Because ALS is a rare disease and prevention is not feasible, treatment that modifies survival is the most realistic strategy. Therefore, identification of modifier genes that might influence ALS survival could improve the understanding of the biology of the disease and suggest biological targets for pharmaceutical intervention. In addition, genetic risk scores for survival could be used as an adjunct to clinical trials to account for the genetic contribution to survival.
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng
653 a Motor-neuron disease
653 a ALS
653 a C9ORF72
653 a Genome-wide association
700a Lin, Kuang4 aut
700a Tiloca, Cinzia4 aut
700a Rooney, James4 aut
700a Gellera, Cinzia4 aut
700a Diekstra, Frank P.4 aut
700a Ratti, Antonia4 aut
700a Shatunov, Aleksey4 aut
700a van Es, Michael A.4 aut
700a Proitsi, Petroula4 aut
700a Jones, Ashley4 aut
700a Sproviero, William4 aut
700a Chio, Adriano4 aut
700a McLaughlin, Russell Lewis4 aut
700a Soraru, Gianni4 aut
700a Corrado, Lucia4 aut
700a Stahl, Daniel4 aut
700a Del Bo, Roberto4 aut
700a Cereda, Cristina4 aut
700a Castellotti, Barbara4 aut
700a Glass, Jonathan D.4 aut
700a Newhouse, Steven4 aut
700a Dobson, Richard4 aut
700a Smith, Bradley N.4 aut
700a Topp, Simon4 aut
700a van Rheenen, Wouter4 aut
700a Meininger, Vincent4 aut
700a Melki, Judith4 aut
700a Morrison, Karen E.4 aut
700a Shaw, Pamela J.4 aut
700a Leigh, P. Nigel4 aut
700a Andersen, Peter M.u Umeå universitet,Klinisk neurovetenskap,Kiel University, Institute of Clinical Molecular Biology, Kiel, Germany4 aut0 (Swepub:umu)pean0001
700a Comi, Giacomo P.4 aut
700a Ticozzi, Nicola4 aut
700a Mazzini, Letizia4 aut
700a D'Alfonso, Sandra4 aut
700a Traynor, Bryan J.4 aut
700a Van Damme, Philip4 aut
700a Robberecht, Wim4 aut
700a Brown, Robert H.4 aut
700a Landers, John E.4 aut
700a Hardiman, Orla4 aut
700a Lewis, Cathryn M.4 aut
700a van den Berg, Leonard H.4 aut
700a Shaw, Christopher E.4 aut
700a Veldink, Jan H.4 aut
700a Silani, Vincenzo4 aut
700a Al-Chalabi, Ammar4 aut
700a Powell, John4 aut
710a Umeå universitetb Klinisk neurovetenskap4 org
773t JAMA Neurologyg 73:7, s. 812-820q 73:7<812-820x 2168-6149x 2168-6157
8564 8u http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-124512x lärosäteslänky Till lärosätets (umu) databas
8564 8u https://doi.org/10.1001/jamaneurol.2016.1114

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