Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
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在创始人队列中确定的肥厚相关多态性应用于心力衰竭风险和死亡率。
DOI：
10.1111/j.1752-8062.2010.00251.x
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Liggett SB
中科院分区：
文献类型：
--
作者：
Parsa A;Chang YP;Kelly RJ;Corretti MC;Ryan KA;Robinson SW;Gottlieb SS;Kardia SL;Shuldiner AR;Liggett SB
采用全基因组、病例对照和仅病例关联研究的三阶段方法来识别与心力衰竭死亡率相关的遗传变异。在阿米什创始人群体 (n = 851) 中，心脏肥大是对失败的适应性反应不可或缺的一个特征，被发现是可遗传的 (h2 = 0.28，p = 0.0002)，并且 GWAS 揭示了 21 个候选肥大 SNP。在一项针对无关白种人的病例 (n = 1,610)-对照 (n = 463) 研究中，与肥大相关的 SNP 之一 (rs2207418, p = 8 × 10−6) 与心力衰竭相关，RR = 1.85(1.25–2.73, p = 0.0019)。在心力衰竭病例中，rs2207418 与死亡率增加相关，HR = 1.51（1.20–1.97，p = 0.0004）。研究之间存在一致性，GG 等位基因与阿米什人心室质量（约 13 g/m2）增加、心力衰竭风险和心力衰竭死亡率相关。该 SNP 位于染色体 20p12 的基因荒漠中。 5 个基因位于 rs2207418 的 2.0 mbp 范围内，但其 SNP 与 rs2207418 之间的 LD 较低。该 SNP 附近的区域在多种脊椎动物中高度保守（lod 得分 = 1,208）。这种保守性和跨研究的内部一致性表明该区域在心力衰竭中具有生物学重要性，可能充当增强子或抑制子元件。 rs2207418 可能有助于预测可能需要积极治疗的更进展形式的心力衰竭。
A three-stage approach was undertaken using genome-wide, case-control, and case-only association studies to identify genetic variants associated with heart failure mortality. In an Amish founder population (n = 851), cardiac hypertrophy, a trait integral to the adaptive response to failure, was found to be heritable (h2 = 0.28, p = 0.0002) and GWAS revealed 21 candidate hypertrophy SNPs. In a case (n = 1,610)-control (n = 463) study in unrelated Caucasians, one of the SNPs associated with hypertrophy (rs2207418, p = 8 × 10−6), was associated with heart failure, RR = 1.85(1.25–2.73, p = 0.0019). In heart failure cases rs2207418 was associated with increased mortality, HR = 1.51(1.20–1.97, p = 0.0004). There was consistency between studies, with the GG allele being associated with increased ventricular mass (~13 g/m2) in the Amish, heart failure risk, and heart failure mortality. This SNP is in a gene desert of chromosome 20p12. Five genes are within 2.0 mbp of rs2207418 but with low LD between their SNPs and rs2207418. A region near this SNP is highly conserved in multiple vertebrates (lod score = 1,208). This conservation and the internal consistency across studies suggests that this region has biologic importance in heart failure, potentially acting as an enhancer or repressor element. rs2207418 may be useful for predicting a more progressive form of heart failure that may require aggressive therapy.
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DOI：
10.1161/circgenetics.109.895995
发表时间：
2010-06
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Morrison AC;Felix JF;Cupples LA;Glazer NL;Loehr LR;Dehghan A;Demissie S;Bis JC;Rosamond WD;Aulchenko YS;Wang YA;Haritunians T;Folsom AR;Rivadeneira F;Benjamin EJ;Lumley T;Couper D;Stricker BH;O'Donnell CJ;Rice KM;Chang PP;Hofman A;Levy D;Rotter JI;Fox ER;Uitterlinden AG;Wang TJ;Psaty BM;Willerson JT;van Duijn CM;Boerwinkle E;Witteman JC;Vasan RS;Smith NL
通讯作者：
Smith NL
DOI：
10.1161/circgenetics.109.895763
发表时间：
2010-06
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Smith NL;Felix JF;Morrison AC;Demissie S;Glazer NL;Loehr LR;Cupples LA;Dehghan A;Lumley T;Rosamond WD;Lieb W;Rivadeneira F;Bis JC;Folsom AR;Benjamin E;Aulchenko YS;Haritunians T;Couper D;Murabito J;Wang YA;Stricker BH;Gottdiener JS;Chang PP;Wang TJ;Rice KM;Hofman A;Heckbert SR;Fox ER;O'Donnell CJ;Uitterlinden AG;Rotter JI;Willerson JT;Levy D;van Duijn CM;Psaty BM;Witteman JC;Boerwinkle E;Vasan RS
通讯作者：
Vasan RS
影响因子：
7
作者：
Siepel, A;Bejerano, G;Haussler, D
通讯作者：
Haussler, D
影响因子：
1.8
作者：
Pollin, Toni I.;McBride, Daniel J.;O'Connell, Jeffrey R.
通讯作者：
O'Connell, Jeffrey R.
影响因子：
5.3
作者：
Sorkin, J;Post, W;Shuldiner, AR
通讯作者：
Shuldiner, AR