Common Variation in Cytoskeletal Genes is Associated with Conotruncal Heart Defects.
Common Variation in Cytoskeletal Genes is Associated with Conotruncal Heart Defects.
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细胞骨架基因的常见变异与圆锥动脉干心脏缺陷有关。
DOI：
10.3390/genes12050655
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发表时间：
2021-04-27
期刊：
影响因子：
3.5
通讯作者：
Mitchell LE
中科院分区：
文献类型：
--
作者：
Musfee FI;Agopian AJ;Goldmuntz E;Hakonarson H;Morrow BE;Taylor DM;Tristani-Firouzi M;Watkins WS;Yandell M;Mitchell LE
有强有力的证据表明，非综合征型先天性心脏病（CHD）的遗传贡献。然而，外显子组和全基因组的研究在变异和基因水平进行了确定几个全基因组显着的CHD相关基因。基因集分析是对这些研究的有益补充，并且罕见变异的候选基因集分析提供了对CHD遗传学的深入了解。然而，尚未使用常见遗传变异的数据进行类似的分析。因此，我们对15个CHD候选基因集进行了常见变异分析，使用了两种常见类型CHD的数据：圆锥动脉干心脏缺损（1431例）和左心室流出道缺损（509例）。在对多个基因集进行Bonferroni校正后，细胞骨架基因集与圆锥动脉干心脏缺陷显著相关（βS = 0.09; 95%置信区间（CI）0.03-0.15）。当分析仅限于在至少两例CHD病例中观察到罕见损伤基因型的细胞骨架基因子集时，这种关联更强（βS = 0.32，95%CI 0.08-0.56）。这些发现增加了细胞骨架基因与冠心病的证据，并表明，细胞骨架基因的共同变异可能有助于冠心病的风险。
There is strong evidence for a genetic contribution to non-syndromic congenital heart defects (CHDs). However, exome- and genome-wide studies conducted at the variant and gene-level have identified few genome-wide significant CHD-related genes. Gene-set analyses are a useful complement to such studies and candidate gene-set analyses of rare variants have provided insight into the genetics of CHDs. However, similar analyses have not been conducted using data on common genetic variants. Consequently, we conducted common variant analyses of 15 CHD candidate gene-sets, using data from two common types of CHDs: conotruncal heart defects (1431 cases) and left ventricular outflow tract defects (509 cases). After Bonferroni correction for evaluation of multiple gene-sets, the cytoskeletal gene-set was significantly associated with conotruncal heart defects (βS = 0.09; 95% confidence interval (CI) 0.03–0.15). This association was stronger when analyses were restricted to the sub-set of cytoskeletal genes that have been observed to harbor rare damaging genotypes in at least two CHD cases (βS = 0.32, 95% CI 0.08–0.56). These findings add to the evidence linking cytoskeletal genes to CHDs and suggest that, for cytoskeletal genes, common variation may contribute to the risk of CHDs.
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影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
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影响因子：
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作者：
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Shendure, Jay
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通讯作者：
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3
作者：
Mägi R;Morris AP
通讯作者：
Morris AP