Sökning: onr:"swepub:oai:lup.lub.lu.se:fbe2089e-e2b7-4665-b777-55c99e6906d6" > Association of LRRK...
Fältnamn | Indikatorer | Metadata |
---|---|---|
000 | 06794naa a2201021 4500 | |
001 | oai:lup.lub.lu.se:fbe2089e-e2b7-4665-b777-55c99e6906d6 | |
003 | SwePub | |
008 | 160401s2011 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:123395582 | |
024 | 7 | a https://lup.lub.lu.se/record/22117072 URI |
024 | 7 | a https://doi.org/10.1016/S1474-4422(11)70175-22 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1233955822 URI |
040 | a (SwePub)lud (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Ross, Owen A.4 aut |
245 | 1 0 | a Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study |
264 | 1 | c 2011 |
520 | a Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng |
700 | 1 | a Soto-Ortolaza, Alexandra I.4 aut |
700 | 1 | a Heckman, Michael G.4 aut |
700 | 1 | a Aasly, Jan O.4 aut |
700 | 1 | a Abahuni, Nadine4 aut |
700 | 1 | a Annesi, Grazia4 aut |
700 | 1 | a Bacon, Justin A.4 aut |
700 | 1 | a Bardien, Soraya4 aut |
700 | 1 | a Bozi, Maria4 aut |
700 | 1 | a Brice, Alexis4 aut |
700 | 1 | a Brighina, Laura4 aut |
700 | 1 | a Van Broeckhoven, Christine4 aut |
700 | 1 | a Carr, Jonathan4 aut |
700 | 1 | a Chartier-Harlin, Marie-Christine4 aut |
700 | 1 | a Dardiotis, Efthimios4 aut |
700 | 1 | a Dickson, Dennis W.4 aut |
700 | 1 | a Diehl, Nancy N.4 aut |
700 | 1 | a Elbaz, Alexis4 aut |
700 | 1 | a Ferrarese, Carlo4 aut |
700 | 1 | a Ferraris, Alessandro4 aut |
700 | 1 | a Fiske, Brian4 aut |
700 | 1 | a Gibson, J. Mark4 aut |
700 | 1 | a Gibson, Rachel4 aut |
700 | 1 | a Hadjigeorgiou, Georgios M.4 aut |
700 | 1 | a Hattori, Nobutaka4 aut |
700 | 1 | a Ioannidis, John P. A.4 aut |
700 | 1 | a Jasinska-Myga, Barbara4 aut |
700 | 1 | a Jeon, Beom S.4 aut |
700 | 1 | a Kim, Yun Joong4 aut |
700 | 1 | a Klein, Christine4 aut |
700 | 1 | a Kruger, Rejko4 aut |
700 | 1 | a Kyratzi, Elli4 aut |
700 | 1 | a Lesage, Suzanne4 aut |
700 | 1 | a Lin, Chin-Hsien4 aut |
700 | 1 | a Lynch, Timothy4 aut |
700 | 1 | a Maraganore, Demetrius M.4 aut |
700 | 1 | a Mellick, George D.4 aut |
700 | 1 | a Mutez, Eugenie4 aut |
700 | 1 | a Nilsson, Christeru Lund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)neur-cni |
700 | 1 | a Opala, Grzegorz4 aut |
700 | 1 | a Park, Sung Sup4 aut |
700 | 1 | a Puschmann, Andreasu Lund University,Lunds universitet,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk neurogenetik,Forskargrupper vid Lunds universitet,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Neurogenetics,Lund University Research Groups4 aut0 (Swepub:lu)med-aps |
700 | 1 | a Quattrone, Aldo4 aut |
700 | 1 | a Sharma, Manu4 aut |
700 | 1 | a Silburn, Peter A.4 aut |
700 | 1 | a Sohn, Young Ho4 aut |
700 | 1 | a Stefanis, Leonidas4 aut |
700 | 1 | a Tadic, Vera4 aut |
700 | 1 | a Theuns, Jessie4 aut |
700 | 1 | a Tomiyama, Hiroyuki4 aut |
700 | 1 | a Uitti, Ryan J.4 aut |
700 | 1 | a Valente, Enza Maria4 aut |
700 | 1 | a van de Loo, Simone4 aut |
700 | 1 | a Vassilatis, Demetrios K.4 aut |
700 | 1 | a Vilarino-Gueell, Cartes4 aut |
700 | 1 | a White, Linda R.4 aut |
700 | 1 | a Wirdefeldt, Karinu Karolinska Institutet4 aut |
700 | 1 | a Wszolek, Zbigniew K.4 aut |
700 | 1 | a Wu, Ruey-Meei4 aut |
700 | 1 | a Farrer, Matthew J.4 aut |
710 | 2 | a Psykiatri, Lundb Sektion IV4 org |
773 | 0 | t Lancet Neurologyg 10:10, s. 898-908q 10:10<898-908x 1474-4465 |
856 | 4 | u http://dx.doi.org/10.1016/S1474-4422(11)70175-2y FULLTEXT |
856 | 4 8 | u https://lup.lub.lu.se/record/2211707 |
856 | 4 8 | u https://doi.org/10.1016/S1474-4422(11)70175-2 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:123395582 |
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
Kopiera och spara länken för att återkomma till aktuell vy