Age of onset and effect size in genome-wide association studies.
Age of onset and effect size in genome-wide association studies.
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全基因组关联研究中的发病年龄和效应大小。
DOI：
10.1002/bdra.23066
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Mitchell,LauraE
中科院分区：
文献类型：
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作者：
Agopian,AJ;Eastcott,LisaM;Mitchell,LauraE
全基因组关联研究（GWAS）已经确定了许多复杂性状的易感基因座，但尚未确定大多数常见疾病的遗传贡献。我们探讨了在GWAS中检测到的关联程度，以及因此在给定样本量下检测到显著关联的可能性，对于儿童期发病的特征（例如，出生缺陷）而不是在成年期发病的特征。方法数据来自国家人类基因组研究所公布的GWAS目录。特征被分类为平均发病年龄在儿童期（<18岁，n = 15个特征）、成年早期（18-54岁，n = 32个特征）或成年晚期（≥55岁，n = 31个特征）。使用logistic回归评估发病年龄类别与GWAS检测到的显著关联程度之间的关系。在校正了几个协变量后，以比值比（OR）≥ 1.5为特征的关联在儿童期特征的GWAS中比成年晚期发病特征显著更常见（校正OR，2.55; 95%置信区间，1.37-4.73）。结果在亚组分析中使用更严格的纳入标准（基于样本量，效应量，纳入的p值阈值，和新的变异性状associations）是similar.CONCLUSIONSThese研究结果表明，平均而言，在GWAS中检测到的标志物性状协会与年轻发病的性状可能有一个更大的幅度的影响比成人发病的性状。因此，GWAS对年轻发病性状，如出生缺陷，可能比成人发病性状更有可能识别主要的遗传风险因素。出生缺陷研究（A部分）2012年。© 2012 Wiley Periodicals，Inc.
BACKGROUNDGenome‐wide association studies (GWAS) have identified many susceptibility loci for complex traits, but have not identified the majority of the genetic contribution to common diseases. We explored whether the magnitude of associations detected in GWAS and, therefore, the likelihood of detecting a significant association for a given sample size, is generally greater for childhood‐onset traits (e.g., birth defects) than for traits with onset in adulthood.METHODSData were obtained from the National Human Genome Research Institute Catalog of Published GWAS. Traits were categorized as having an average age of onset in childhood (<18 years, n = 15 traits), early adulthood (18–54 years, n = 32 traits), or late adulthood (≥55 years, n = 31 traits). The relationship between age of onset category and the magnitude of significant associations detected by GWAS was assessed using logistic regression.RESULTSAssociations characterized by an odds ratio (OR) ≥ 1.5 were significantly more common for GWAS of childhood traits than for late adulthood‐onset traits after adjustment for several covariates (adjusted OR, 2.55; 95% confidence interval, 1.37–4.73). Results in subgroup analyses using more stringent inclusion criteria (based on sample size, effect size,pvalue threshold for inclusion, and novel variant‐trait associations) were similar.CONCLUSIONSThese findings suggest that, on average, marker‐trait associations detected in GWAS for traits with young onset may have a larger magnitude of effect than those for traits with adult onset. Therefore, GWAS for young‐onset traits, such as birth defects, may be more likely than those for adult‐onset traits to identify major genetic risk factors. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.