Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.
| Title: | Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome. |
|---|---|
| Authors: | Lahrouchi, N; Tadros, R; Crotti, L; Mizusawa, Y; Postema, PG; Beekman, L; Walsh, R; Hasegawa, K; Barc, J; Ernsting, M; Turkowski, KL; Mazzanti, A; Beckmann, BM; Shimamoto, K; Diamant, U-B; Wijeyeratne, YD; Kucho, Y; Robyns, T; Ishikawa, T; Arbelo, E; Christiansen, M; Winbo, A; Jabbari, R; Lubitz, SA; Steinfurt, J; Rudic, B; Loeys, B; Shoemaker, MB; Weeke, PE; Pfeiffer, R; Davies, B; Andorin, A; Hofman, N; Dagradi, F; Pedrazzini, M; Tester, DJ; Bos, JM; Sarquella-Brugada, G; Campuzano, Ó; Platonov, PG; Stallmeyer, B; Zumhagen, S; Nannenberg, EA; Veldink, JH; van den Berg, LH; Al-Chalabi, A; Shaw, CE; Shaw, PJ; Morrison, KE; Andersen, PM; Müller-Nurasyid, M; Cusi, D; Barlassina, C; Galan, P; Lathrop, M; Munter, M; Werge, T; Ribasés, M; Aung, T; Khor, CC; Ozaki, M; Lichtner, P; Meitinger, T; van Tintelen, JP; Hoedemaekers, Y; Denjoy, I; Leenhardt, A; Napolitano, C; Shimizu, W; Schott, J-J; Gourraud, J-B; Makiyama, T; Ohno, S; Itoh, H; Krahn, AD; Antzelevitch, C; Roden, DM; Saenen, J; Borggrefe, M; Odening, KE; Ellinor, PT; Tfelt-Hansen, J; Skinner, JR; van den Berg, MP; Olesen, MS; Brugada, J; Brugada, R; Makita, N; Breckpot, J; Yoshinaga, M; Behr, ER; Rydberg, A; Aiba, T; Kääb, S; Priori, SG; Guicheney, P; Tan, HL; Newton-Cheh, C; Ackerman, MJ; Schwartz, PJ; Schulze-Bahr, E; Probst, V; Horie, M; Wilde, AA; Tanck, MWT; Bezzina, CR |
| Publisher Information: | American Heart Association |
| Publication Year: | 2020 |
| Collection: | St George's University of London: Repository |
| Description: | 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 |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf; application/vnd.ms-excel |
| Language: | English |
| ISSN: | 1524-4539 |
| Relation: | https://openaccess.sgul.ac.uk/id/eprint/111978/12/CIRCULATIONAHA.120.045956.pdf; https://openaccess.sgul.ac.uk/id/eprint/111978/1/Lahrouchi-LQTS-GWAS-Manuscript-accepted.pdf; https://openaccess.sgul.ac.uk/id/eprint/111978/6/Lahrouchi-LQTS-GWAS-Supplements.pdf; https://openaccess.sgul.ac.uk/id/eprint/111978/11/Lahrouchi-LQTS-GWAS-Supplementary-Tables-accepted.xlsx; Lahrouchi, N; Tadros, R; Crotti, L; Mizusawa, Y; Postema, PG; Beekman, L; Walsh, R; Hasegawa, K; Barc, J; Ernsting, M; et al. Lahrouchi, N; Tadros, R; Crotti, L; Mizusawa, Y; Postema, PG; Beekman, L; Walsh, R; Hasegawa, K; Barc, J; Ernsting, M; Turkowski, KL; Mazzanti, A; Beckmann, BM; Shimamoto, K; Diamant, U-B; Wijeyeratne, YD; Kucho, Y; Robyns, T; Ishikawa, T; Arbelo, E; Christiansen, M; Winbo, A; Jabbari, R; Lubitz, SA; Steinfurt, J; Rudic, B; Loeys, B; Shoemaker, MB; Weeke, PE; Pfeiffer, R; Davies, B; Andorin, A; Hofman, N; Dagradi, F; Pedrazzini, M; Tester, DJ; Bos, JM; Sarquella-Brugada, G; Campuzano, Ó; Platonov, PG; Stallmeyer, B; Zumhagen, S; Nannenberg, EA; Veldink, JH; van den Berg, LH; Al-Chalabi, A; Shaw, CE; Shaw, PJ; Morrison, KE; Andersen, PM; Müller-Nurasyid, M; Cusi, D; Barlassina, C; Galan, P; Lathrop, M; Munter, M; Werge, T; Ribasés, M; Aung, T; Khor, CC; Ozaki, M; Lichtner, P; Meitinger, T; van Tintelen, JP; Hoedemaekers, Y; Denjoy, I; Leenhardt, A; Napolitano, C; Shimizu, W; Schott, J-J; Gourraud, J-B; Makiyama, T; Ohno, S; Itoh, H; Krahn, AD; Antzelevitch, C; Roden, DM; Saenen, J; Borggrefe, M; Odening, KE; Ellinor, PT; Tfelt-Hansen, J; Skinner, JR; van den Berg, MP; Olesen, MS; Brugada, J; Brugada, R; Makita, N; Breckpot, J; Yoshinaga, M; Behr, ER; Rydberg, A; Aiba, T; Kääb, S; Priori, SG; Guicheney, P; Tan, HL; Newton-Cheh, C; Ackerman, MJ; Schwartz, PJ; Schulze-Bahr, E; Probst, V; Horie, M; Wilde, AA; Tanck, MWT; Bezzina, CR (2020) Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome. Circulation, 142 (4). pp. 324-338. ISSN 1524-4539 https://doi.org/10.1161/CIRCULATIONAHA.120.045956 SGUL Authors: Behr, Elijah Raphael |
| Availability: | https://openaccess.sgul.ac.uk/id/eprint/111978/; https://openaccess.sgul.ac.uk/id/eprint/111978/12/CIRCULATIONAHA.120.045956.pdf |
| Rights: | cc_by_nc_nd_4 |
| Accession Number: | edsbas.2BD36B7C |
| Database: | BASE |