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(WFRF:(Lewis Cathryn M)) srt2:(2015-2019)
 

Search: (WFRF:(Lewis Cathryn M)) srt2:(2015-2019) > Association of a Lo...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006022naa a2200913 4500
001oai:DiVA.org:umu-124512
003SwePub
008160815s2016 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1245122 URI
0247 a 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
1001 a Fogh, Isabella4 aut
2451 0a Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis
264 1b American Medical Association (AMA),c 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 MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
653 a Motor-neuron disease
653 a ALS
653 a C9ORF72
653 a Genome-wide association
7001 a Lin, Kuang4 aut
7001 a Tiloca, Cinzia4 aut
7001 a Rooney, James4 aut
7001 a Gellera, Cinzia4 aut
7001 a Diekstra, Frank P.4 aut
7001 a Ratti, Antonia4 aut
7001 a Shatunov, Aleksey4 aut
7001 a van Es, Michael A.4 aut
7001 a Proitsi, Petroula4 aut
7001 a Jones, Ashley4 aut
7001 a Sproviero, William4 aut
7001 a Chio, Adriano4 aut
7001 a McLaughlin, Russell Lewis4 aut
7001 a Soraru, Gianni4 aut
7001 a Corrado, Lucia4 aut
7001 a Stahl, Daniel4 aut
7001 a Del Bo, Roberto4 aut
7001 a Cereda, Cristina4 aut
7001 a Castellotti, Barbara4 aut
7001 a Glass, Jonathan D.4 aut
7001 a Newhouse, Steven4 aut
7001 a Dobson, Richard4 aut
7001 a Smith, Bradley N.4 aut
7001 a Topp, Simon4 aut
7001 a van Rheenen, Wouter4 aut
7001 a Meininger, Vincent4 aut
7001 a Melki, Judith4 aut
7001 a Morrison, Karen E.4 aut
7001 a Shaw, Pamela J.4 aut
7001 a Leigh, P. Nigel4 aut
7001 a Andersen, Peter M.u Umeå universitet,Klinisk neurovetenskap,Kiel University, Institute of Clinical Molecular Biology, Kiel, Germany4 aut0 (Swepub:umu)pean0001
7001 a Comi, Giacomo P.4 aut
7001 a Ticozzi, Nicola4 aut
7001 a Mazzini, Letizia4 aut
7001 a D'Alfonso, Sandra4 aut
7001 a Traynor, Bryan J.4 aut
7001 a Van Damme, Philip4 aut
7001 a Robberecht, Wim4 aut
7001 a Brown, Robert H.4 aut
7001 a Landers, John E.4 aut
7001 a Hardiman, Orla4 aut
7001 a Lewis, Cathryn M.4 aut
7001 a van den Berg, Leonard H.4 aut
7001 a Shaw, Christopher E.4 aut
7001 a Veldink, Jan H.4 aut
7001 a Silani, Vincenzo4 aut
7001 a Al-Chalabi, Ammar4 aut
7001 a Powell, John4 aut
7102 a Umeå universitetb Klinisk neurovetenskap4 org
7730 t JAMA Neurologyd : American Medical Association (AMA)g 73:7, s. 812-820q 73:7<812-820x 2168-6149x 2168-6157
8564 u https://jamanetwork.com/journals/jamaneurology/articlepdf/2525542/noi160035.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-124512
8564 8u https://doi.org/10.1001/jamaneurol.2016.1114

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