Data-driven phenotype discovery of FMR1 premutation carriers in a population-based sample
Data-driven phenotype discovery of FMR1 premutation carriers in a population-based sample
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DOI：
10.1126/sciadv.aaw7195
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发表时间：
2019-08-01
期刊：
影响因子：
13.6
通讯作者：
Mailick, Marsha R.
中科院分区：
文献类型：
--
作者：
Movaghar, Arezoo;Page, David;Mailick, Marsha R.
FMR 1前突变对人类健康的影响是相当有争议的主题。一个基本的未回答的问题是携带前突变等位基因是否与临床表型直接相关。以往FMR 1前突变的基因型-表型研究中存在的一个挑战性问题是确定偏倚，这可能导致无效的研究结论，并对临床实践产生负面影响。在这里，我们创建了第一个基于人群的FMR 1信息生物库，以发现前突变携带者的健康特征模式。我们广泛的表型分析表明，前突变携带者的临床表现与对照组明显不同，并且在整个成年期都很明显。全面了解与这种遗传变异相关的临床风险对前突变携带者、其家庭和临床医生至关重要，并对公共卫生具有重要意义。
The impact of the FMR1 premutation on human health is the subject of considerable controversy. A fundamental unanswered question is whether carrying the premutation allele is directly correlated with clinical phenotypes. A challenging problem in past genotype-phenotype studies of the FMR1 premutation is ascertainment bias, which could lead to invalid research conclusions and negatively affect clinical practice. Here, we created the first population-based FMR1-informed biobank to find the pattern of health characteristics in premutation carriers. Our extensive phenotyping shows that premutation carriers experience a clinical profile that is significantly different from controls and is evident throughout adulthood. Comprehensive understanding of the clinical risk associated with this genetic variant is critical for premutation carriers, their families, and clinicians and has important implications for public health.