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- Huyghe, Jeroen R., et al.
(författare)
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Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait
- 2008
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 83:3, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.
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- McAuliffe, Carmel, et al.
(författare)
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Problem-solving ability and repetition of deliberate self-harm : a multicentre study.
- 2006
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 36:1, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- Background. While recent studies have found problem-solving impairments in individuals who engage in deliberate self-harm (DSH), few studies have examined repeaters and non-repeaters separately. The aim of the present study was to investigate whether specific types of problem-solving are associated with repeated DSH. Method. As part of the WHO/EURO Multicentre Study on Suicidal Behaviour, 836 medically treated DSH patients (59% repeaters) from 12 European regions were interviewed using the European Parasuicide Study Interview Schedule (EPSIS II) approximately 1 year after their index episode. The Utrecht Coping List (UCL) assessed habitual responses to problems. Results. Factor analysis identified five dimensions – Active Handling, Passive-Avoidance, Problem Sharing, Palliative Reactions and Negative Expression. Passive-Avoidance – characterized by a pre-occupation with problems, feeling unable to do anything, worrying about the past and taking a gloomy view of the situation, a greater likelihood of giving in so as to avoid difficult situations, the tendency to resign oneself to the situation, and to try to avoid problems – was the problem-solving dimension most strongly associated with repetition, although this association was attenuated by self-esteem. Conclusions. The outcomes of the study indicate that treatments for DSH patients with repeated episodes should include problem-solving interventions. The observed passivity and avoidance of problems (coupled with low self-esteem) associated with repetition suggests that intensive therapeutic input and follow-up are required for those with repeated DSH.
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- Van Laer, Lut, et al.
(författare)
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The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment
- 2008
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 17:2, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Age-related hearing impairment (ARHI) is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. The contribution of various environmental factors has been relatively extensively studied. In contrast, investigations to identify the genetic risk factors have only recently been initiated. In this paper we describe the results of an association study performed on 2418 ARHI samples derived from nine centers from seven European countries. In 70 candidate genes, a total of 768 tag single nucleotide polymorphisms (SNPs) were selected based on HAPMAP data. These genes were chosen among the monogenic hearing loss genes identified in mice and men in addition to several strong functional candidates. After genotyping and data polishing, statistical analysis of all samples combined resulted in a P-value that survived correction for multiple testing for one SNP in the GRHL2 gene. Other SNPs in this gene were also associated, albeit to a lesser degree. Subsequently, an analysis of the most significant GRHL2 SNP was performed separately for each center. The direction of the association was identical in all nine centers. Two centers showed significant associations and a third center showed a trend towards significance. Subsequent fine mapping of this locus demonstrated that the majority of the associated SNPs reside in intron 1. We hypothesize that the causative variant may change the expression levels of a GRHL2 isoform.
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