Sökning: onr:"swepub:oai:DiVA.org:umu-174908" > Transethnic Genome-...
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000 | 09805naa a2201717 4500 | |
001 | oai:DiVA.org:umu-174908 | |
003 | SwePub | |
008 | 200911s2020 | |||||||||||000 ||eng| | |
009 | oai:lup.lub.lu.se:ad6ffbaa-ae0f-4f96-8700-738d7ed561cd | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1749082 URI |
024 | 7 | a https://doi.org/10.1161/CIRCULATIONAHA.120.0459562 DOI |
024 | 7 | a https://lup.lub.lu.se/record/ad6ffbaa-ae0f-4f96-8700-738d7ed561cd2 URI |
040 | a (SwePub)umud (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Lahrouchi, Najimu University of Amsterdam,Academic Medical Center of University of Amsterdam (AMC)4 aut |
245 | 1 0 | a Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome |
264 | 1 | b Lippincott Williams & Wilkins,c 2020 |
338 | a electronic2 rdacarrier | |
520 | a Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
653 | a genome-wide association study | |
653 | a inheritance patterns | |
653 | a long QT syndrome | |
653 | a genome-wide association study | |
653 | a inheritance patterns | |
653 | a long QT syndrome | |
700 | 1 | a Tadros, Rafik4 aut |
700 | 1 | a Crotti, Lia4 aut |
700 | 1 | a Mizusawa, Yuka4 aut |
700 | 1 | a Postema, Pieter G.4 aut |
700 | 1 | a Beekman, Leander4 aut |
700 | 1 | a Walsh, Roddy4 aut |
700 | 1 | a Hasegawa, Kanae4 aut |
700 | 1 | a Barc, Julien4 aut |
700 | 1 | a Ernsting, Marko4 aut |
700 | 1 | a Turkowski, Kari L.4 aut |
700 | 1 | a Mazzanti, Andrea4 aut |
700 | 1 | a Beckmann, Britt M.4 aut |
700 | 1 | a Shimamoto, Keiko4 aut |
700 | 1 | a Diamant, Ulla-Brittu Umeå universitet,Pediatrik,European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart4 aut0 (Swepub:umu)uldi0001 |
700 | 1 | a Wijeyeratne, Yanushi D.4 aut |
700 | 1 | a Kucho, Yu4 aut |
700 | 1 | a Robyns, Tomas4 aut |
700 | 1 | a Ishikawa, Taisuke4 aut |
700 | 1 | a Arbelo, Elena4 aut |
700 | 1 | a Christiansen, Michael4 aut |
700 | 1 | a Winbo, Annika4 aut |
700 | 1 | a Jabbari, Reza4 aut |
700 | 1 | a Lubitz, Steven A.4 aut |
700 | 1 | a Steinfurt, Johannes4 aut |
700 | 1 | a Rudic, Boris4 aut |
700 | 1 | a Loeys, Bart4 aut |
700 | 1 | a Shoemaker, M. Ben4 aut |
700 | 1 | a Weeke, Peter E.4 aut |
700 | 1 | a Pfeiffer, Ryan4 aut |
700 | 1 | a Davies, Brianna4 aut |
700 | 1 | a Andorin, Antoine4 aut |
700 | 1 | a Hofman, Nynke4 aut |
700 | 1 | a Dagradi, Federica4 aut |
700 | 1 | a Pedrazzini, Matteo4 aut |
700 | 1 | a Tester, David J.4 aut |
700 | 1 | a Bos, J. Martijn4 aut |
700 | 1 | a Sarquella-Brugada, Georgia4 aut |
700 | 1 | a Campuzano, Oscar4 aut |
700 | 1 | a Platonov, Pyotru Lund University,Lunds universitet,Electrocardiology Research Group - CIEL,Forskargrupper vid Lunds universitet,Lund University Research Groups4 aut0 (Swepub:lu)kard-ppl |
700 | 1 | a Stallmeyer, Birgit4 aut |
700 | 1 | a Zumhagen, Sven4 aut |
700 | 1 | a Nannenberg, Eline A.4 aut |
700 | 1 | a Veldink, Jan H.4 aut |
700 | 1 | a van den Berg, Leonard H.4 aut |
700 | 1 | a Al-Chalabi, Ammar4 aut |
700 | 1 | a Shaw, Christopher E.4 aut |
700 | 1 | a Shaw, Pamela J.4 aut |
700 | 1 | a Morrison, Karen E.4 aut |
700 | 1 | a Andersen, Peter M.,d 1962-u Umeå universitet,Klinisk neurovetenskap,Department of Neurology, Ulm University, Germany (P.M.A.)4 aut0 (Swepub:umu)pean0001 |
700 | 1 | a Mueller-Nurasyid, Martina4 aut |
700 | 1 | a Cusi, Daniele4 aut |
700 | 1 | a Barlassina, Cristina4 aut |
700 | 1 | a Galan, Pilar4 aut |
700 | 1 | a Lathrop, Mark4 aut |
700 | 1 | a Munter, Markus4 aut |
700 | 1 | a Werge, Thomas4 aut |
700 | 1 | a Ribases, Marta4 aut |
700 | 1 | a Aung, Tin4 aut |
700 | 1 | a Khor, Chiea C.4 aut |
700 | 1 | a Ozaki, Mineo4 aut |
700 | 1 | a Lichtner, Peter4 aut |
700 | 1 | a Meitinger, Thomas4 aut |
700 | 1 | a van Tintelen, J. Peter4 aut |
700 | 1 | a Hoedemaekers, Yvonne4 aut |
700 | 1 | a Denjoy, Isabelle4 aut |
700 | 1 | a Leenhardt, Antoine4 aut |
700 | 1 | a Napolitano, Carlo4 aut |
700 | 1 | a Shimizu, Wataru4 aut |
700 | 1 | a Schott, Jean-Jacques4 aut |
700 | 1 | a Gourraud, Jean-Baptiste4 aut |
700 | 1 | a Makiyama, Takeru4 aut |
700 | 1 | a Ohno, Seiko4 aut |
700 | 1 | a Itoh, Hideki4 aut |
700 | 1 | a Krahn, Andrew D.4 aut |
700 | 1 | a Antzelevitch, Charles4 aut |
700 | 1 | a Roden, Dan M.4 aut |
700 | 1 | a Saenen, Johan4 aut |
700 | 1 | a Borggrefe, Martin4 aut |
700 | 1 | a Odening, Katja E.4 aut |
700 | 1 | a Ellinor, Patrick T.4 aut |
700 | 1 | a Tfelt-Hansen, Jacob4 aut |
700 | 1 | a Skinner, Jonathan R.4 aut |
700 | 1 | a van den Berg, Maarten P.4 aut |
700 | 1 | a Olesen, Morten Salling4 aut |
700 | 1 | a Brugada, Josep4 aut |
700 | 1 | a Brugada, Ramon4 aut |
700 | 1 | a Makita, Naomasa4 aut |
700 | 1 | a Breckpot, Jeroen4 aut |
700 | 1 | a Yoshinaga, Masao4 aut |
700 | 1 | a Behr, Elijah R.4 aut |
700 | 1 | a Rydberg, Annikau Umeå universitet,Pediatrik,European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart4 aut0 (Swepub:umu)anry0014 |
700 | 1 | a Aiba, Takeshi4 aut |
700 | 1 | a Kaeaeb, Stefan4 aut |
700 | 1 | a Priori, Silvia G.4 aut |
700 | 1 | a Guicheney, Pascale4 aut |
700 | 1 | a Tan, Hanno L.4 aut |
700 | 1 | a Newton-Cheh, Christopher4 aut |
700 | 1 | a Ackerman, Michael J.4 aut |
700 | 1 | a Schwartz, Peter J.4 aut |
700 | 1 | a Schulze-Bahr, Eric4 aut |
700 | 1 | a Probst, Vincent4 aut |
700 | 1 | a Horie, Minoru4 aut |
700 | 1 | a Wilde, Arthur A.4 aut |
700 | 1 | a Tanck, Michael W. T.4 aut |
700 | 1 | a Bezzina, Connie R.u Academic Medical Center of University of Amsterdam (AMC)4 aut |
710 | 2 | a University of Amsterdamb Academic Medical Center of University of Amsterdam (AMC)4 org |
710 | 2 | a et al. |
773 | 0 | t Circulationd : Lippincott Williams & Wilkinsg 142:4, s. 324-338q 142:4<324-338x 0009-7322x 1524-4539 |
856 | 4 | u https://doi.org/10.1161/CIRCULATIONAHA.120.045956y Fulltext |
856 | 4 | u https://umu.diva-portal.org/smash/get/diva2:1466263/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 | u http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045956x freey FULLTEXT |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-174908 |
856 | 4 8 | u https://doi.org/10.1161/CIRCULATIONAHA.120.045956 |
856 | 4 8 | u https://lup.lub.lu.se/record/ad6ffbaa-ae0f-4f96-8700-738d7ed561cd |
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