Ji-Young Lee1,2, Tae-Hoon Kim1, Pil-Sung Yang1, Hong Euy Lim3, Eue-Keun Choi4, Jaemin Shim5, Eunsoon Shin6, Jae-Sun Uhm1, Jin-Seok Kim3, Boyoung Joung1, Seil Oh4, Moon-Hyoung Lee1, Young-Hoon Kim5, Hui-Nam Pak1,2. 1. Division of Cardiology, Department of Internal Medicine, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. 2. Cardiovascular Genome Center, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. 3. Division of Cardiology, Cardiovascular Center, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea. 4. Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. 5. Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, 73 Inchon-Ro, Seongbuk-gu, Seoul 02841, Republic of Korea. 6. DNA Link Incorporaton, 150 Bugahyeon-ro, Seodaemun-gu, Seoul 03759, Republic of Korea.
Abstract
AIMS: Some genetic susceptibility loci for atrial fibrillation (AF) identified by genome-wide association studies (GWAS) in a European database showed ethnic differences in the Asian population. We explored novel AF susceptibility variants for patients with early-onset AF (≤60 years old) among Korean patients who underwent AF catheter ablation. METHODS AND RESULTS: A genome-wide association study (GWAS) was conducted with 672 cases (≤60 years old, Yonsei AF Ablation cohort) and 3700 controls (Korea Genome Epidemiology Study). Association analysis was performed under an additive model of logistic regression, and replication study was conducted with 200 independent cases of Korean AF Network and 1812 controls. Five previously proven genetic loci (1q24/PRRX1, 4q25/PITX2, 10q24/NEURL, 12q24/TBX5, and 16q22/ZFHX3) were validated. Two novel genetic loci associated with early-onset AF were found on chromosomes 1q32.1/PPFIA4 (rs11579055, P = 6.84 × 10-10) and 4q34.1/HAND2 (rs8180252, P = 1.49 × 10-11) and replicated in an additional independent sample of the Korean AF Network. The identified loci implicate candidate genes that encode proteins related to cell-to-cell connection, hypoxic status, or long non-coding RNA. CONCLUSION: Two novel genetic loci for early-onset AF were identified in Korean patients who underwent catheter ablation. One of the novel susceptibility loci on chromosome 4 has strong associations with previously proven gene in a European ancestry database. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Some genetic susceptibility loci for atrial fibrillation (AF) identified by genome-wide association studies (GWAS) in a European database showed ethnic differences in the Asian population. We explored novel AF susceptibility variants for patients with early-onset AF (≤60 years old) among Korean patients who underwent AF catheter ablation. METHODS AND RESULTS: A genome-wide association study (GWAS) was conducted with 672 cases (≤60 years old, Yonsei AF Ablation cohort) and 3700 controls (Korea Genome Epidemiology Study). Association analysis was performed under an additive model of logistic regression, and replication study was conducted with 200 independent cases of Korean AF Network and 1812 controls. Five previously proven genetic loci (1q24/PRRX1, 4q25/PITX2, 10q24/NEURL, 12q24/TBX5, and 16q22/ZFHX3) were validated. Two novel genetic loci associated with early-onset AF were found on chromosomes 1q32.1/PPFIA4 (rs11579055, P = 6.84 × 10-10) and 4q34.1/HAND2 (rs8180252, P = 1.49 × 10-11) and replicated in an additional independent sample of the Korean AF Network. The identified loci implicate candidate genes that encode proteins related to cell-to-cell connection, hypoxic status, or long non-coding RNA. CONCLUSION: Two novel genetic loci for early-onset AF were identified in Korean patients who underwent catheter ablation. One of the novel susceptibility loci on chromosome 4 has strong associations with previously proven gene in a European ancestry database. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Seung Hoan Choi; Sean J Jurgens; Lu-Chen Weng; James P Pirruccello; Carolina Roselli; Mark Chaffin; Christina J-Y Lee; Amelia W Hall; Amit V Khera; Kathryn L Lunetta; Steven A Lubitz; Patrick T Ellinor Journal: Circ Res Date: 2019-11-06 Impact factor: 17.367
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