Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

<p>Abstract</p> <p>Background</p> <p>Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients.</p> <p>Methods</p> <p>We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA).</p> <p>Results</p> <p>No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients.</p> <p>Conclusions</p> <p>Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.</p

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3–50, P < 2.14 × 10−6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-d-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach

Cancer mortality in Aboriginal people in New South Wales, Australia, 1994-2002

OBJECTIVE: To describe, for the first time, mortality from cancer for Aboriginal residents of New South Wales (NSW). METHODS: These are the results of a descriptive study of cancer deaths from the NSW Central Cancer Registry for 1994 to 2002. Standardised mortality ratios were calculated with Poisson confidence intervals to compare the relative rates in the Indigenous and non-Indigenous populations. RESULTS: The overall standardised mortality rates were 66% higher for males and 59% higher for females for Aboriginal people compared with non-Indigenous people. Mortality from lung cancer was 50% and 100% higher than for NSW non-Indigenous males and females respectively. The high mortality rate from cervical cancer in Aboriginal females is contrary to the trends in the general population since the introduction of free population-based screening. CONCLUSIONS: For the first time, data are available for cancer mortality for Aboriginal people in NSW. Mortality for all cancers combined was higher than that of the non-Indigenous population. This suggests that a combination of later diagnoses and perhaps poorer treatment outcomes as well as being diagnosed with poorer prognosis cancers is occurring in Aboriginal people of NSW. IMPLICATIONS: It was possible to increase the rate of identification in a population register using routinely collected data, but the completeness and accuracy of Indigenous status should, and can, be improved in all notifying data collections. Public health planners in NSW can now begin to address the issues of prevention, treatment and palliation of cancer in Aboriginal people with local, rather than imputed, evidenc

Rheumatic heart disease in pregnancy: Strategies and lessons learnt implementing a population-based study in Australia

© The Author(s) 2018. Background: The global burden of rheumatic heart disease (RHD) is two-to-four times higher in women, with a heightened risk in pregnancy. In Australia, RHD is found predominantly among Aboriginal and Torres Strait Islander peoples. Methods: This paper reviews processes developed to identify pregnant Australian women with RHD during a 2-year population-based study using the Australasian Maternity Outcomes Surveillance System (AMOSS). It evaluates strategies developed to enhance reporting and discusses implications for patient care and public health. Results: AMOSS maternity coordinators across 262 Australian sites reported cases. An extended network across cardiac, Aboriginal and primary healthcare strengthened surveillance and awareness. The network notified 495 potential cases, of which 192 were confirmed. Seventy-eight per cent were Aboriginal and/or Torres Strait Islander women, with a prevalence of 22 per 1000 in the Northern Territory. Discussion: Effective surveillance was challenged by a lack of diagnostic certainty, incompatible health information systems and varying clinical awareness among health professionals. Optimal outcomes for pregnant women with RHD demand timely diagnosis and access to collaborative care. Conclusion: The strategies employed by this study highlight gaps in reporting processes and the opportunity pregnancy provides for diagnosis and re/engagement with health services to support better continuity of care and promote improved outcomes

Extreme morbid obesity in pregnancy: Risk management and resources

Background: The Australasian Maternity Outcomes Surveillance System (AMOSS) combines a clinical and population-based health approach to study the burden and outcomes of rare and serious conditions in pregnancy. The aim of this study was to determine the incidence and health service impact of extreme obesity in pregnancy in Australia and New Zealand (ANZ). Method: Morbid obesity was defined as >140 kg and/or a BMI > 50 at any point during pregnancy. De-identified data were collected from eligible maternity units (>50 births/year) throughout ANZ via a secure web-based survey system during 2010. A separate web-survey covering issues related to policies and management of extreme obesity in pregnancy was administered to maternity units. Results: Preliminary results show an incidence of 1.7/1000 women (n = 307) who gave birth had extreme morbid obesity. Mean age of 30 years (range 17—47 years) and 38% were primiparous. 51% gave birth by caesarean section. Women were not routinely weighed at antenatal booking in 17% of cases. The majority of hospitals (72%) rated the resource burden on their units as medium/high for managing extreme morbid obesity. Risk management processes varied, and 63% of maternity unit responded that there was no referral process to a special clinic or risk management process for pregnant women with extreme morbid obesity. In comments about management, 22% of maternity unit respondents expressed concern about existing policies related to risk management and transfer. Conclusions: There are significant challenges in providing quality care for women with extreme morbid obesity in pregnancy related to risk management, policies and available resources

Ethical issues: The multi-centre low-risk ethics/governance review process and AMOSS

Background: The Australasian Maternity Outcomes Surveillance System (AMOSS) conducts surveillance and research of rare and serious conditions in pregnancy. This multi-centre population health study is considered low risk with minimal ethical impact. Objective: To describe the ethics/governance review pathway undertaken by AMOSS. Method: Prospective, descriptive study during 2009-2011 of the governance/ethical review processes required to gain approval for Australian and New Zealand (ANZ) maternity units with more than 50 births per year (n = 303) to participate in AMOSS. Results: Review processes ranged from a single application for 24 NZ sites, a single application for eligible hospitals in two Australian states, full Health Research Ethics Committee (HREC) applications for individual hospitals, through simple letters of support. As of September 2011, 46 full/expedited ethics applications, 131 site governance applications and 136 letters of support requests were made over 33 months, involving an estimated 3261 hours by AMOSS staff/investigators, and an associated resource burden by participating sites, to obtain approval to receive nonidentifiable data from 291 hospitals. Conclusion: The AMOSS research system provides an important resource to enhance knowledge of conditions that cause rare and serious maternal morbidity. Yet the highly variable ethical approval processes required to implement this study have been excessively repetitive and burdensome. This process jeopardises timely, efficient research project implementation, without corresponding benefits to research participants. The resource burden to establish research governance for AMOSS confirms the urgent need for the Harmonisation of Multi-centre Ethical Review (HoMER) to further streamline ethics/governance review processes for multi-centre research. © 2012 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists