Data-driven phenotype discovery of FMR1 premutation carriers in a population-based sample
Open Access
- 2 August 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 5 (8), eaaw7195
- https://doi.org/10.1126/sciadv.aaw7195
Abstract
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.Keywords
Funding Information
- National Human Genome Research Institute (UO1HG8701)
- National Institute of Child Health and Human Development (U54 HD090256)
- National Institute of Child Health and Human Development (R01 HD082110)
- National Center for Advancing Translational Sciences (UL1TR000427)
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