Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families

A recent report showed significant associations between several SNPs in a previously unknown EST cluster with schizophrenia. (1). The cluster was identified as the human dystrobrevin binding protein 1 gene (DTNBP1) by sequence database comparisons and homology with mouse DTNBP1. (2). However, the linkage disequilibrium (LD) among the SNPs in DTNBP1 as well as the pattern of significant SNP-schizophrenia association was complex. This raised several questions such as the number of susceptibility alleles that may be involved and the size of the region where the actual disease mutation(s) could be located. To address these questions, we performed different single-marker tests on the 12 previously studied and 2 new SNPs in DTNBP1 that were re-scored using an improved procedure, and performed a variety of haplotype analyses. The sample consisted of 268 Irish multiplex families selected for high density of schizophrenia. Results suggested a simple structure where the LD in the target region could be explained by 6 haplotypes that together accounted for 96% of haplotype diversity in the whole sample. From these six, a single high-risk haplotype was identified that showed a significant association with schizophrenia and explained the pattern of significant findings in the analyses with individual markers. This haplotype was 30 kb long, had a large effect, could be measured with two tag SNPs only, had a frequency of 6% in our sample, seemed to be of relatively recent origin in evolutionary terms, and was equally distributed over Ireland. Implications of these findings for follow-up and replication studies are discussed.

Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families

The enzyme catechol-o-methyltransferase (COMT) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of COMT with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP rs4680, which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs rs737865-rs4680-rs165599, was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that COMT gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects.

No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF)

The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

Regulator of G-protein signaling 4 (RGS4) gene is associated with schizophrenia in Irish high density families

The regulator of the G-protein signaling 4 (RGS4) gene was shown to have a different expression pattern in schizophrenia patients in a microarray study. A family-based study subsequently implicated the association of this gene with schizophrenia. We replicated the study with our sample from the Irish Study of High Density Schizophrenia Families (ISHDSF). Single marker transmission disequilibrium tests (TDT) for the four core SNPs showed modest association for SNP 18 (using a narrow diagnostic approach with FBAT P = 0.044; with PDT P = 0.0073) and a trend for SNP 4 (with FBAT P = 0.1098; with PDT P = 0.0249). For SNP 1 and 7, alleles overtransmitted to affected subjects were the same as previously reported. Haplotype analyses suggested that haplotype G-G-G for SNP1-4-18, which is the most abundant haplotype (42.3%) in the Irish families, was associated with the disease (narrow diagnosis, FBAT P = 0.0061, PDT P = 0.0498). This was the same haplotype implicated in the original study. While P values were not corrected for multiple testing because of the clear prior hypothesis, these results could be interpreted as supporting evidence for the association between RGS4 and schizophrenia.

Evaluation of genetic substructure in the Irish Study of High-Density Schizophrenia Families

The presence of genetic substructure has the potential to diminish the chances of detecting a linkage signal. Using a Markov chain Monte Carlo procedure developed by Pritchard and colleagues and implemented in the program STRUCTURE, we evaluated the evidence for genetic substructure using genotypes from 37 microsatellite markers in affected individuals selected at random from 263 multiplex families in the Irish Study of High-Density Schizophrenia Families. We found no evidence for the presence of genetic substructure in this sample.

‘My city’s million voices chiding me’::‘Answerability’ and Modern Irish Working-Class Writers

Published as part of a special edition on working-class writers, this article explores the work of Paula Meehan, Martin Lynch and Dermot Bolger.

Assessing suspended sediment dynamics in relation to ecological thresholds and sampling strategies in two Irish headwater catchments

Prediction of the impact of suspended sediment on aquatic ecosystems requires adequate knowledge of sediment dynamics in surface waters. Often, studies reporting the response of aquatic biota to suspended sediment are concerned with concentrations, while catchment erosion studies often report sediment delivery as annual loads and yields, making the comparison to documented ecological impacts difficult. Similarly, the European Union Freshwater Fish Directive (FFD) (78/659/EC) stipulates a guideline value of 25mgl which should not be exceeded, with the exception of floods and droughts. In this respect, the significance of suspended sediment in two Irish rivers was assessed using turbidity sensors calibrated for suspended sediment. Sediment yields of 0.07 tonnes (t) hayear and 0.44thayear and annual FFD exceedance frequency of 8.3% and 17.8% were estimated for the two catchments. Contrasts in the frequency of exceedance events between both catchments was observed, yet duration was typically short (

On Irish stickleback:Morphological diversification in a secondary contact zone

Question: How parallel is adaptive evolution when it occurs from different genetic backgrounds? Background: Divergent evolutionary lineages of several post-glacial fish species including the threespine stickleback are found together in Ireland. Goals: To investigate the morphological diversity of stickleback populations in Ireland and assess whether morphology evolved in parallel between evolutionary lineages. Methods: We sampled stickleback from lake, river, and coastal habitats across Ireland. Microsatellite and mitochondrial DNA data revealed evolutionary history. Geometric morphometrics and linear trait measurements characterized morphology. We used a multivariate approach to quantify parallel and non-parallel divergence within and between lineages. Results: Repeated evolution of similar morphologies in similar habitats occurred across Ireland, concordant with patterns observed elsewhere in the stickleback distribution. A strong pattern of habitat-specific morphology existed even among divergent lineages. Furthermore, a strong signal of shared morphological divergence occurred along a marine-freshwater axis. Evidently, deterministic natural selection played a more important role in driving freshwater adaptation than independent evolutionary history. © 2013 Mark Ravinet.

Consideration of future consequences and alcohol use among Northern Irish adolescents

This study investigated the relationship between consideration of future consequences and alcohol use among adolescents. A cross-sectional design was used and a large sample of 12-to 16-year-old schoolchildren (n = 806) in Northern Ireland were recruited for this study. Alcohol use was assessed using a composite measure of drinking behaviour, the Adolescent Alcohol Involvement Scale. Time perspective was measured using the Consideration of Future Consequences Scale (CFCS). Data were also gathered on self-esteem, three domains of self-efficacy and aggression, all of which have been found to be related to both drinking behaviour and time perspective. Factor analysis of the CFCS revealed support for a two-factor solution, with CFC-I representing present orientation and CFC-F representing future orientation. After controlling for year in school (proxy for age) and gender and for clustering at school level, scores on both subscales were significantly associated with alcohol use. Only CFC-F score remained significant with the addition of psychosocial variables. These results support recent findings of a significant relationship between CFCS score and alcohol use in UK adolescents and University undergraduates, and suggest that in more fully controlled analyses, future orientation, rather than present, is related to adolescent drinking. Results are discussed in relation to health promotion. © 2013 Informa UK Ltd.

Investigation of failures in Irish raised bogs

This paper presents the results of field geophysical testing and laboratory testing of peat from Carn Park and Roosky raised bogs in the Irish Midlands. The motivation for the work was highlight the importance of these areas and to begin to attempt to understand the reasons for the failure of the bogs despite them having surface slopes of some 1°. It was found that the peat is typical of that of Irish raised bogs being up to 8m thick towards the “high” dome of the bogs. The peat is characterised by low density, high water content, high organic content, low undrained shear strength and high compressibility. The peat is also relatively permeable at in situ stress. Geophysical electrical resistivity tomography and ground penetrating radar data shows a clear thinning of the peat in the area of the failures corresponding to a reduction in volume from dewatering by edge drains/peat harvesting. This finding is supported by detailed water content measurements. It was also shown that the peat base topography is relatively flat and indicates that the observed surface movement has come from within the peat rather than from the material below the peat. Potential causes of the failures include conventional slope instability, the effect of seepage forces or the release of built-up gas in the peat mass. Further measurements are required in order to study these in more detail.