04206nas a2200889 4500008004100000022001400041245008500055210006900140260001600209520162400225100002001849700002501869700002501894700002901919700002301948700003001971700001502001700002202016700001502038700002002053700002102073700002202094700001902116700001702135700002202152700002102174700001902195700002202214700001802236700002202254700002302276700002202299700002602321700001702347700001802364700001202382700002302394700002102417700001802438700001902456700002002475700002202495700002202517700002402539700002302563700003002586700002002616700002402636700002402660700002802684700001902712700002502731700002502756700002002781700002402801700002702825700002202852700002702874700002402901700002202925700002002947700001802967700002002985700002303005700001803028700002303046700002203069700001903091700001903110700001903129700002003148700002403168700001903192700002203211710004703233856003603280 2018 eng d a1522-964500aA comprehensive evaluation of the genetic architecture of sudden cardiac arrest.0 acomprehensive evaluation of the genetic architecture of sudden c c2018 Aug 283 a
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.
1 aAshar, Foram, N1 aMitchell, Rebecca, N1 aAlbert, Christine, M1 aNewton-Cheh, Christopher1 aBrody, Jennifer, A1 aMüller-Nurasyid, Martina1 aMoes, Anna1 aMeitinger, Thomas1 aMak, Angel1 aHuikuri, Heikki1 aJunttila, Juhani1 aGoyette, Philippe1 aPulit, Sara, L1 aPazoki, Raha1 aTanck, Michael, W1 aBlom, Marieke, T1 aZhao, XiaoQing1 aHavulinna, Aki, S1 aJabbari, Reza1 aGlinge, Charlotte1 aTragante, Vinicius1 aEscher, Stefan, A1 aChakravarti, Aravinda1 aEhret, Georg1 aCoresh, Josef1 aLi, Man1 aPrineas, Ronald, J1 aFranco, Oscar, H1 aKwok, Pui-Yan1 aLumley, Thomas1 aDumas, Florence1 aMcKnight, Barbara1 aRotter, Jerome, I1 aLemaitre, Rozenn, N1 aHeckbert, Susan, R1 aO'Donnell, Christopher, J1 aHwang, Shih-Jen1 aTardif, Jean-Claude1 aVanDenburgh, Martin1 aUitterlinden, André, G1 aHofman, Albert1 aStricker, Bruno, H C1 ade Bakker, Paul, I W1 aFranks, Paul, W1 aJansson, Jan-Håkan1 aAsselbergs, Folkert, W1 aHalushka, Marc, K1 aMaleszewski, Joseph, J1 aTfelt-Hansen, Jacob1 aEngstrøm, Thomas1 aSalomaa, Veikko1 aVirmani, Renu1 aKolodgie, Frank1 aWilde, Arthur, A M1 aTan, Hanno, L1 aBezzina, Connie, R1 aEijgelsheim, Mark1 aRioux, John, D1 aJouven, Xavier1 aKääb, Stefan1 aPsaty, Bruce, M1 aSiscovick, David, S1 aArking, Dan, E1 aSotoodehnia, Nona1 aSCD working group of the CHARGE Consortium uhttps://chs-nhlbi.org/node/7778