Integrating genetic, transcriptional, and functional analyses to identify five novel genes for atrial fibrillation.
- Sinner, M.F.
- Tucker, N.R.
- Lunetta, K.L.
- Ozaki, K.
- Smith, J.G.
- Trompet, S.
- Bis, J.C.
- Lin, H.
- Chung, M.K.
- Nielsen, J.B.
- Lubitz, S.A.
- Krijthe, B.P.
- Magnani, J.W.
- Ye, J.
- Gollob, M.H.
- Tsunoda, T.
- Müller-Nurasyid, M.
- Lichtner, P.
- Peters, A.
- Dolmatova, E.
- Kubo, M.
- Smith, J.D.
- Psaty, B.M.
- Smith, N.L.
- Jukema, J.W.
- Chasman, D.I.
- Albert, C.M.
- Ebana, Y.
- Furukawa, T.
- Macfarlane, P.W.
- Harris, T.B.
- Darbar, D.
- Dörr, M.
- Holst, A.G.
- Svendsen, J.H.
- Hofman, A.
- Uitterlinden, A.
- Gudnason, V.
- Isobe, M.
- Malik, R.
- Dichgans, M.
- Rosand, J.
- van Wagoner, D.R.
- METASTROKE Consortium (Kääb, S.)
- AFGen Consortium (Ellinor, P.T.)
- Benjamin, E.J.
- Milan, D.J.
- Melander, O.
- Heckbert, S.R
- Ford, I.
- Liu, Y.
- Barnard, J.
- Olesen, M.S.
- Stricker, B.H.
- Tanaka, T.
DOIAbstract
BACKGROUND: -Atrial fibrillation (AF) affects over 30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: -To identify new AF-related genes, we utilized a multifaceted approach, combining large-scale genotyping in two ethnically distinct populations, cis-eQTL mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501, RR=1.18, 95%CI 1.13 - 1.23, p=6.5x10(-16)), GJA1 (rs13216675, RR=1.10, 95%CI 1.06 - 1.14, p=2.2x10(-8)), TBX5 (rs10507248, RR=1.12, 95%CI 1.08 - 1.16, p=5.7x10(-11)), and CAND2 (...
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