Genome-Wide Variants Associated With Longitudinal Survival Outcomes Among Individuals With Coronary Artery Disease.
Genome-Wide Variants Associated With Longitudinal Survival Outcomes Among Individuals With Coronary Artery Disease.
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DOI：
10.3389/fgene.2021.661497
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发表时间：
2021
影响因子：
3.7
通讯作者：
Kraus WE
中科院分区：
文献类型：
--
作者：
Dungan JR;Qin X;Hurdle M;Haynes CS;Hauser ER;Kraus WE
冠状动脉疾病（CAD）是一种与年龄相关的疾病，大大增加了死亡风险。本研究的目的是通过全基因组筛选方法，在临床表型型CAD患者中确定与全因死亡率相关的基因变异。我们使用来自杜克导管遗传学生物库的两个GWAS子研究的CAD白人患者的次要数据，对基因组变异与生存结果的关联进行了发现（n = 684）、复制（n = 1088）和荟萃分析（n = 1503）。我们使用Cox多变量回归分析对从置管到死亡或最后一次随访的时间（中位7.1年，最长12年）进行建模。目标统计筛选阈值在发现阶段为p × 10-8，在复制阶段为bonferroni计算的p值（p < 5.3 × 10-4）和荟萃分析阶段（p < 1.6 × 10-3）。对785,945个常染色体snp的全基因组分析显示，两个snp （rs13007553和rss587936）在分析的所有三个阶段都具有相同的影响方向，在发现和复制方面具有提示性的p值关联，并且在调整临床协变量的模型中具有显著的meta分析相关性。位于MYTIL和EIPR1之间的rs13007553 SNP变体LINC01250，即使在控制了临床协变量后，也会增加全因死亡的风险[HR 1.47, 95% CI 1.17-1.86, p(adj) = 1.07 × 10-3（发现），p(adj) = 0.03（复制），p(adj) = 9.53 × 10-5（荟萃分析）]。MYT1L参与神经元分化。TSSC1参与内体循环并与乳腺癌有关。注释到DAB2IP的rs587936变异与生存时间增加相关[HR 0.65, 95% CI 0.51-0.83, p(adj) = 4.79 × 10-4（发现），p(adj) = 0.02（复制），p(adj) = 2.25 × 10-5（荟萃分析）]。DAB2IP是一种在血管组织中高表达的ras/GAP肿瘤抑制基因。DAB2IP有多种预防动脉粥样硬化的证据。重复的研究结果确定了两个与高危CAD患者生存相关的候选基因：新的基因座LINC01250 （rs13007553）和生物学相关的候选基因DAB2IP （rs587936）。这些候选基因与已证实的长寿候选基因没有重叠。未来的研究可以进一步确定常见变异在冠心病患者生存结果中的作用，并最终改善这些患者的纵向结果。
Coronary artery disease (CAD) is an age-associated condition that greatly increases the risk of mortality. The purpose of this study was to identify gene variants associated with all-cause mortality among individuals with clinically phenotyped CAD using a genome-wide screening approach. We performed discovery (n = 684), replication (n = 1,088), and meta-analyses (N = 1,503) for association of genomic variants with survival outcome using secondary data from White participants with CAD from two GWAS sub-studies of the Duke Catheterization Genetics Biorepository. We modeled time from catheterization to death or last follow-up (median 7.1 years, max 12 years) using Cox multivariable regression analysis. Target statistical screening thresholds were p × 10–8 for the discovery phase and Bonferroni-calculated p-values for the replication (p < 5.3 × 10–4) and meta-analysis (p < 1.6 × 10–3) phases. Genome-wide analysis of 785,945 autosomal SNPs revealed two SNPs (rs13007553 and rs587936) that had the same direction of effect across all three phases of the analysis, with suggestive p-value association in discovery and replication and significant meta-analysis association in models adjusted for clinical covariates. The rs13007553 SNP variant, LINC01250, which resides between MYTIL and EIPR1, conferred increased risk for all-cause mortality even after controlling for clinical covariates [HR 1.47, 95% CI 1.17–1.86, p(adj) = 1.07 × 10–3 (discovery), p(adj) = 0.03 (replication), p(adj) = 9.53 × 10–5 (meta-analysis)]. MYT1L is involved in neuronal differentiation. TSSC1 is involved in endosomal recycling and is implicated in breast cancer. The rs587936 variant annotated to DAB2IP was associated with increased survival time [HR 0.65, 95% CI 0.51–0.83, p(adj) = 4.79 × 10–4 (discovery), p(adj) = 0.02 (replication), p(adj) = 2.25 × 10–5 (meta-analysis)]. DAB2IP is a ras/GAP tumor suppressor gene which is highly expressed in vascular tissue. DAB2IP has multiple lines of evidence for protection against atherosclerosis. Replicated findings identified two candidate genes for further study regarding association with survival in high-risk CAD patients: novel loci LINC01250 (rs13007553) and biologically relevant candidate DAB2IP (rs587936). These candidates did not overlap with validated longevity candidate genes. Future research could further define the role of common variants in survival outcomes for people with CAD and, ultimately, improve longitudinal outcomes for these patients.
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影响因子：
1.5
作者：
Ivanova AA;Maksimov VN;Orlov PS;Ivanoshchuk DE;Savchenko SV;Voevoda MI
通讯作者：
Voevoda MI
DOI：
10.1161/circgenetics.110.957928
发表时间：
2011-04
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Anderson CD;Nalls MA;Biffi A;Rost NS;Greenberg SM;Singleton AB;Meschia JF;Rosand J
通讯作者：
Rosand J
影响因子：
4.5
作者：
Kraus WE;Muoio DM;Stevens R;Craig D;Bain JR;Grass E;Haynes C;Kwee L;Qin X;Slentz DH;Krupp D;Muehlbauer M;Hauser ER;Gregory SG;Newgard CB;Shah SH
通讯作者：
Shah SH
影响因子：
2.1
作者：
Aouizerat BE;Vittinghoff E;Musone SL;Pawlikowska L;Kwok PY;Olgin JE;Tseng ZH
通讯作者：
Tseng ZH
SDF1多态性影响症状性心血管疾病患者的结果。
影响因子：
3.7
作者：
Rath D;Schaeffeler E;Winter S;Hewer J;Müller K;Droppa M;Stimpfle F;Gawaz M;Schwab M;Geisler T
通讯作者：
Geisler T