Investigation of Phenotypes Associated with Mood and Anxiety Among Male and Female Fragile X Premutation Carriers
ABSTRACT The fragile X disorder spectrum, due to a CGG expansion in FMR1, includes fragile X syndrome (>200 repeats) and the premutation-associated disorders of ovarian insufficiency and tremor/ataxia
syndrome (~55–199 repeats). Altered neurobehavioral profiles including variation of phenotypes associated with mood and anxiety
may be expected among younger premutation carriers given this spectrum of disorders. However, previous studies have produced
conflicting findings, providing the motivation to examine these phenotypes further. We investigated measures of mood and anxiety
in 119 males and 446 females age 18–50 ascertained from families with a history of fragile X syndrome and from the general
population. Scores were analyzed using a linear model with repeat length as the main predictor, adjusting for potential confounders.
Repeat length was not associated with anxiety, but was marginally associated with depression and negative affect in males
and negative affect only in females. These results suggest that premutation carriers may be at risk for emotional morbidity;
however, phenotypic differences were subtle and of small effect size.
- SourceAvailable from: PubMed CentralGenetics in Medicine 3(3):200-5. · 5.56 Impact Factor
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ABSTRACT: Although previous studies have suggested that the fragile X premutation (fra [X] pM) does not cause deleterious effects, methodological constraints have prevented more definitive conclusions from being reached. In this report, we describe the neuropsychiatric and cognitive-neuropsychological status of 34 adult women with the fra (X) pM, as compared with a well-matched control group of 41 mothers of fra (X)-negative children with developmental disability. The results indicate that there are no meaningful differences between adult women with the fra (X) pM and control subjects with respect to cognitive abilities or profile, neuropsychological function, psychiatric diagnoses or symptoms, and self-rated personality profile. No measure for either group showed evidence of functioning outside the normal range except for a high lifetime prevalence of major depression in both groups. Additional exploratory analyses within the fra (X) group showed no significant effect of either the size of the fra (X) insert or X chromosome inactivation pattern in leukocytes, on any measure of neurobehavioral function. These findings provide additional information to professionals providing genetic counseling to, and assessment of, fra (X) families.The American Journal of Human Genetics 06/1993; 52(5):884-94. · 11.20 Impact Factor
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ABSTRACT: In this report, we describe a simple correction for multiple testing of single-nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with each other, on the basis of the spectral decomposition (SpD) of matrices of pairwise LD between SNPs. This method provides a useful alternative to more computationally intensive permutation tests. A user-friendly interface (SNPSpD) for performing this correction is available online (http://genepi.qimr.edu.au/general/daleN/SNPSpD/). Additionally, output from SNPSpD includes eigenvalues, principal-component coefficients, and factor "loadings" after varimax rotation, enabling the selection of a subset of SNPs that optimize the information in a genomic region.The American Journal of Human Genetics 05/2004; 74(4):765-9. · 11.20 Impact Factor