A comprehensive evaluation of the genetic architecture of sudden cardiac arrest.

Ashar, Foram N; Mitchell, Rebecca N; Albert, Christine M; Newton-Cheh, Christopher; Brody, Jennifer A; Müller-Nurasyid, Martina; Moes, Anna; Meitinger, Thomas; Mak, Angel; Huikuri, Heikki; Junttila, M Juhani; Goyette, Philippe; Pulit, Sara L; Pazoki, Raha; Tanck, Michael W; Blom, Marieke T; Zhao, XiaoQing; Havulinna, Aki S; Jabbari, Reza; Glinge, Charlotte; ... (2018). A comprehensive evaluation of the genetic architecture of sudden cardiac arrest. European Heart Journal, 39(44), pp. 3961-3969. Oxford University Press 10.1093/eurheartj/ehy474

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Aims Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. Methods and results We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk. Conclusions Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Franco Duran, Oscar Horacio

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

0195-668X

Publisher:

Oxford University Press

Language:

English

Submitter:

Tanya Karrer

Date Deposited:

13 Sep 2018 09:31

Last Modified:

23 Nov 2018 01:31

Publisher DOI:

10.1093/eurheartj/ehy474

PubMed ID:

30169657

BORIS DOI:

10.7892/boris.119859

URI:

https://boris.unibe.ch/id/eprint/119859

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