ANKH and susceptibility to and severity of ankylosing spondylitis

Objective. Unconfirmed reports describe association of ankylosing spondylitis (AS) with several candidate genes including ANKH. Cellular export of inorganic pyrophosphate is regulated by the ANK protein, and mutant mice (ank/ank), which have a premature stop codon in the 3′ end of the ank gene, develop severe ankylosis. We tested the association between single-nucleotide polymorphisms (SNP) in these genes and susceptibility to AS in a population of patients with AS. We investigated the role of these genes in terms of functional (BASFI) and metrological (BASMI) measures, and the association with radiological severity (mSASSS). Methods. Our study was conducted on 355 patients with AS and 95 ethnically matched healthy controls. AS was defined according to the modified New York criteria. Four SNP in ANKH (rs27356, rs26307, rs25957, and rs28006) were genotyped. Association analysis was performed using Cochrane-Armitage and linear regression tests for dichotomous and quantitative variables. Analyses of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASFI, and mSASSS were controlled for sex and disease duration. Results. None of the 4 markers showed significant single-locus disease associations (p > 0.05), suggesting that ANKH was not a major determinant of AS susceptibility in our population. No association was observed between these SNP and age at symptom onset, BASDAI, BASFI, BASMI, or mSASSS. Conclusion. These results confirm data in white Europeans that ANKH is probably not a major determinant of susceptibility to AS. ANKH polymorphisms do not markedly influence AS disease severity, as measured by BASMI and mSASSS. The Journal of Rheumatology

Predominant association of HLA-B*2704 with ankylosing spondylitis in Chinese Han patients

The HLA-B27 subtypes have a varied racial and ethnic prevalence throughout the world. However, the association of B27-subtypes with ankylosing spondylitis (AS) in the mainland China is unknown. To determine the association of B27-subtypes with AS in the Mainland Chinese Han population, a total of unrelated 153 patients with AS were enrolled in a large case-control association study, and 1545 unrelated, healthy, ethnically matched blood donors were included as controls. The genotyping of B27 and its subtypes was performed using the polymerase chain reaction with sequence specific primers (PCR-SSP). A total of 130 (84.97%) AS patients and 61 (3.95%) healthy controls were B27 positive. Three B27-subtypes, B*2704, B*2705 and B*2710, were further identified, of which both B*2704 and B*2705 were strongly AS associated. B*2710 was only detected in one AS patient and two other healthy controls. Considering only B27-positive cases and controls, a statistically different frequency of B27-subtypes was observed, with an over-representation of B*2704 (P = 0.018). B*2704 was clearly more strongly associated than B*2705 with AS [odds ratio (OR) = 2.4, P = 0.011]. Furthermore, a combined analysis including three previous studies of B27-subtype distributions in Chinese AS cases confirmed the stronger association of B*2704 with AS than B*2705 (OR = 2.5, P = 0.00094).

The Sapphires

Synopsis and critique of Indigenous musical comedy, The Saphhires, directed by Wayne Blair.

Impact of ethnicity upon body composition assessment in Sri Lankan Australian children

Objectives: Obesity is a disease with excess body fat where health is adversely affected. Therefore it is prudent to make the diagnosis of obesity based on the measure of percentage body fat. Body composition of a group of Australian children of Sri Lankan origin were studied to evaluate the applicability of some bedside techniques in the measurement of percentage body fat. Methods: Height (H) and weight (W) was measured and BMI (W/H2) calculated. Bioelectrical impedance analysis (BIA) was measured using tetra polar technique with an 800 μA current of 50 Hz frequency. Total body water was used as a reference method and was determined by deuterium dilution and fat free mass and hence fat mass (FM) derived using age and gender specific constants. Percentage FM was estimated using four predictive equations, which used BIA and anthropometric measurements. Results: Twenty-seven boys and 15 girls were studied with mean ages being 9.1 years and 9.6 years, respectively. Girls had a significantly higher FM compared to boys. The mean percentage FM of boys (22.9 ± 8.7%) was higher than the limit for obesity and for girls (29.0 ± 6.0%) it was just below the cut-off. BMI was comparatively low. All but BIA equation in boys under estimated the percentage FM. The impedance index and weight showed a strong association with total body water (r 2 = 0.96, P < 0.001). Except for BIA in boys all other techniques under diagnosed obesity. Conclusions: Sri Lankan Australian children appear to have a high percentage of fat with a low BMI and some of the available indirect techniques are not helpful in the assessment of body composition. Therefore ethnic and/or population specific predictive equations have to be developed for the assessment of body composition, especially in a multicultural society using indirect methods such as BIA or anthropometry.

HLA-DR/DQ haplotype in rheumatoid arthritis: Novel allelic associations in UK Caucasians

Objective. To elucidate the relative importance of the HLA-DR and HLA-DQ loci in conferring genetic predisposition to rheumatoid arthritis (RA). Methods. HLA-DRB1 and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence-specific polymerase chain reaction. Allele and phenotype frequencies were compared with those in 2 large sets of historical, ethnically matched healthy controls, using the relative predispositional effect method. Results. Positive association was confirmed with the shared epitope positive HLA-DRB1 alleles associated with RA in Caucasians. A significant susceptibility effect was observed with HLA-DRB1*09, described in other ethnically diverse populations but not in Caucasians. A significant underrepresentation of the HLA-DRB1*0103 variant was noted among the RA cases, supporting the proposed protective role of the DERAA motif at residues 70-74 of the DRβ molecule. No HLA-DRB1 independent association of the HLA-DQB1 alleles, implicated in predisposing to RA, was evident. Conclusion. These data corroborate the shared epitope hypothesis of susceptibility to RA and provide strong evidence for the DRB1 locus as the primary RA susceptibility factor in the HLA region.

Interethnic studies of TNF polymorphisms confirm the likely presence of a second MHC susceptibility locus in ankylosing spondylitis

The objective of this study was to investigate TNF promoter region polymorphisms for association with susceptibility to ankylosing spondylitis (AS). The TNF -238 and -308 polymorphisms were genotyped in 306 English AS cases and 204 ethnically matched healthy B27-positive controls, and 96 southern German AS cases, 58 B27-positive and 251 B27-negative ethnically matched controls. Additionally, the TNF -376 polymorphism was genotyped in the southern German cases and controls. In the southern German AS patients a significant reduction in TNF -308.2 alleles was seen, compared with B27 positive controls (odds ratio 0.4, P= 0.03, 95% confidence interval 0.2-0.9), but no difference in allele frequencies was observed at TNF -238. Significant association between AS and both TNF -238 and TNF -308 was excluded in the English cases. These results confirm previous observations in the southern German population of association between TNF promoter region polymorphisms and AS, but the lack of association in the English population suggests that these polymorphisms themselves are unlikely to be directly involved. More likely, a second, non-HLA-B, MHC locus is involved in susceptibility to AS in these two populations.

Sri Lankan entrepreneurs in Australia: Chance or choice?

Purpose Ethnic entrepreneurship is, and always has been, a means of survival. However, there is limited literature on ethnic entrepreneurship in Australia and therefore, an understanding of ethnic entrepreneurs’ motivations to become self-employed. The purpose of this paper is to report the influential factors in the decision to engage in self-employment through case studies of members of Melbourne’s Sri Lankan community informed by the mixed embeddedness approach. Design/methodology/approach The mixed embeddedness approach frames the study where the authors examine the motivations for business of five Sri Lankan entrepreneurs. Narratives are used to construct individual case studies, which are then analyzed in terms of the motivations for, resources used and challenges faced on the entrepreneurial journey. Findings For these ethnic entrepreneurs, their entrepreneurial activity results from a dynamic match between local market opportunities and the specific ethnic resources available to them at the time of founding. The self-employment decision was not prompted by a lack of human capital but an inability to use that human capital in alternative means of employment at specific points in time. Moreover the authors highlight the importance of social and cultural capital as resources used to overcome challenges on the entrepreneurial journey. Originality/value In this community, entrepreneurship was not a result of a lack of human capital but how it was utilized in combination with social and cultural capitals in the given opportunity structure. The mixed embeddedness approach enables the uncovering of how ethnic network ties were used in light of the opportunities available to build entrepreneurial activity.

Association of NOS1AP variants and depression phenotypes in schizophrenia

Background The nitric oxide synthase 1 adaptor protein gene (NOS1AP) has previously been recognised as a schizophrenia susceptibility gene due to its role in glutamate neurotransmission. The gene is believed to inhibit nitric oxide (NO) production activated by the N-methyl-d-aspartate (NMDA) receptor and reduced NO levels have been observed in schizophrenia patients. However, association studies investigating NOS1AP and schizophrenia have produced inconsistent results, most likely because schizophrenia is a clinically heterogeneous disorder. This study aims to investigate the association between NOS1AP variants and defined depression phenotypes of schizophrenia. Methods Nine NOS1AP SNPs, rs1415259, rs1415263, rs1858232, rs386231, rs4531275, rs4656355, rs4657178, rs6683968 and rs6704393 were genotyped in 235 schizophrenia subjects screened for various phenotypes of depression. Result One NOS1AP SNP (rs1858232) was associated with the broad diagnosis of schizophrenia and eight SNPs were associated with depression related phenotypes within schizophrenia. The rs1415259 SNP showed strong association with sleep dysregulation phenotypes of depression. Conclusion Results suggest that NOS1AP variants are associated with various forms of depression in schizophrenia and are more prevalent in males. Limitation Schizophrenia is a clinically heterogeneous disease that can vary greatly between different ethnic and geographic populations so our observations should be viewed with caution until they are independently replicated, particularly in larger patient cohorts.

Generalizability of established prostate cancer risk variants in men of African ancestry

Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

Governance and regional variation of homicide rates: Evidence from cross-national data

Criminological theories of cross-national studies of homicide have underestimated the effects of quality governance of liberal democracy and region. Data sets from several sources are combined and a comprehensive model of homicide is proposed. Results of the spatial regression model, which controls for the effect of spatial autocorrelation, show that quality governance, human development, economic inequality, and ethnic heterogeneity are statistically significant in predicting homicide. In addition, regions of Latin America and non-Muslim Sub-Saharan Africa have significantly higher rates of homicides ceteris paribus while the effects of East Asian countries and Islamic societies are not statistically significant. These findings are consistent with the expectation of the new modernization and regional theories.

What is racism? Othering, prejudice and hate-motivated violence

The paper’s concern is the current difficulty, in journalism, the academy and politics, of discussing questions to do with race, ethnicity, difference and immigration because of the fear of being called a racist. It starts with an analysis of biographical interview data drawn from fifteen people who had variously acquired the label racist and who were part of a small-scale study into racism in the Midlands city of Stoke-on-Trent, UK conducted between 2003 and 2005. The interviews used the free association narrative interview method. This analysis revealed that most people do not consider themselves racist and that having a conviction for a racially aggravated offence or being a member of a far right organisation was not able to differentiate racists from non-racists. It also revealed a spectrum of attitudes towards immigrants or particular ethnic groups: strong expressions of hatred at one end of the spectrum; strong prejudicial feelings in the middle; and a feeling that ‘outsider’ groups should not benefit at the expense of ‘insiders’ (called ‘othering’) at the other end. The turn to theory for assistance revealed that, although hatred, prejudice and ‘othering’ are not the same thing, and do not have the same origins, they have become elided. This is primarily because cognitive psychology’s hostility to psychoanalysis marginalised hatred whilst its exclusive preoccupation with prejudice came effectively to define racism at the individual level. Progress in thinking about racism might consist of abolishing the term and returning to thinking about hatred, prejudice and ‘othering’ separately.

Mobility and security: the perceived benefits of citizenship for resettled young people from refugee backgrounds

In recent decades, the meaning and value of formal state citizenship has shifted dramatically. In the same period, scholarship on citizenship has drawn attention to the proliferation of alternative forms of sub-, supra- and transnational citizenship, at times obscuring the ongoing importance of formal state citizenship. For refugees, however, formal state citizenship remains a critical and widely shared goal. Drawing on interviews with 51 young people from refugee backgrounds in Melbourne, Australia, this article explores the intersecting themes of mobility and security that were identified by participants as the most important benefits of acquiring formal state citizenship in the country of resettlement. In contrast to the insecurity of forced migration, formal state citizenship provides a privileged mobility that enables refugee-background youth to maintain and create transnational identities and attachments and to be protected while doing so, while also granting a secure status within the nation state and insurance against further displacement in an uncertain future. In offering these forms of mobility and security, formal state citizenship contributes to a sense of ontological security among refugee-background youth, providing an important foundation for building national and transnational futures.

Association between endometriosis and the interleukin 1A (IL1A) locus

STUDY QUESTION Are single-nucleotide polymorphisms (SNPs) at the interleukin 1A (IL1A) gene locus associated with endometriosis risk? SUMMARY ANSWER We found evidence for strong association between IL1A SNPs and endometriosis risk. WHAT IS KNOWN ALREADY Genetic factors contribute substantially to the complex aetiology of endometriosis and the disease has an estimated heritability of ∼51%. We, and others, have conducted genome-wide association (GWA) studies for endometriosis, which identified a total of nine independent risk loci. Recently, two small Japanese studies reported eight SNPs (rs6542095, rs11677416, rs3783550, rs3783525, rs3783553, rs2856836, rs1304037 and rs17561) at the IL1A gene locus as suggestively associated with endometriosis risk. There is also evidence of a link between inflammation and endometriosis. STUDY DESIGN, SIZE, DURATION We sought to further investigate the eight IL1A SNPs for association with endometriosis using an independent sample of 3908 endometriosis cases and 8568 controls of European and Japanese ancestry. The study was conducted between October 2013 and July 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS By leveraging GWA data from our previous multi-ethnic GWA meta-analysis for endometriosis, we imputed variants in the IL1A region, using a recent 1000 Genomes reference panel. After combining summary statistics for the eight SNPs from our European and Japanese imputed data with the published results, a fixed-effect meta-analysis was performed. An additional meta-analysis restricted to endometriosis cases with moderate-to-severe (revised American Fertility Society stage 3 or 4) disease versus controls was also performed. MAIN RESULTS AND THE ROLE OF CHANCE All eight IL1A SNPs successfully replicated at P < 0.014 in the European imputed data with concordant direction and similar size to the effects reported in the original Japanese studies. Of these, three SNPs (rs6542095, rs3783550 and rs3783525) also showed association with endometriosis at a nominal P < 0.05 in our independent Japanese sample. Fixed-effect meta-analysis of the eight SNPs for moderate-to-severe endometriosis produced a genome-wide significant association for rs6542095 (odds ratio = 1.21; 95% confidence interval = 1.13–1.29; P = 3.43 × 10−8). LIMITATIONS, REASONS FOR CAUTION The meta-analysis for moderate-to-severe endometriosis included results of moderate-to-severe endometriosis cases from our European data sets and all endometriosis cases from the Japanese data sets, as disease stage information was not available for endometriosis cases in the Japanese data sets. WIDER IMPLICATIONS OF THE FINDINGS SNP rs6542095 is located ∼2.3 kb downstream of the IL1A gene and ∼6.9 kb upstream of cytoskeleton-associated protein 2-like (CKAP2L) gene. The IL1A gene encodes the IL1a protein, a member of the interleukin 1 cytokine family which is involved in various immune responses and inflammatory processes. These results provide important replication in an independent Japanese sample and, for the first time, association of the IL1A locus in endometriosis patients of European ancestry. SNPs within the IL1A locus may regulate other genes, but if IL1A is the target, our results provide supporting evidence for a link between inflammatory responses and the pathogenesis of endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

Genome-wide linkage and association analyses implicate FASN in predisposition to Uterine Leiomyomata

Uterine leiomyomata (UL), the most prevalent pelvic tumors in women of reproductive age, pose a major public health problem given their high frequency, associated morbidities, and most common indication for hysterectomies. A genetic component to UL predisposition is supported by analyses of ethnic predisposition, twin studies, and familial aggregation. A genome-wide SNP linkage panel was genotyped and analyzed in 261 white UL-affected sister-pair families from the Finding Genes for Fibroids study. Two significant linkage regions were detected in 10p11 (LOD = 4.15) and 3p21 (LOD = 3.73), and five additional linkage regions were identified with LOD scores > 2.00 in 2q37, 5p13, 11p15, 12q14, and 17q25. Genome-wide association studies were performed in two independent cohorts of white women, and a meta-analysis was conducted. One SNP (rs4247357) was identified with a p value (p = 3.05 x 10(-8)) that reached genome-wide significance (odds ratio = 1.299). The candidate SNP is under a linkage peak and in a block of linkage disequilibrium in 17q25.3, which spans fatty acid synthase (FASN), coiled-coil-domain-containing 57 (CCDC57), and solute-carrier family 16, member 3 (SLC16A3). By tissue microarray immunohistochemistry, we found elevated (3-fold) FAS levels in UL-affected tissue compared to matched myometrial tissue. FAS transcripts and/or protein levels are upregulated in various neoplasms and implicated in tumor cell survival. FASN represents the initial UL risk allele identified in white women by a genome-wide, unbiased approach and opens a path to management and potential therapeutic intervention.