Community-based Suicide Prevention Research in Remote On-Reserve First Nations Communities

Suicide is a complex problem linked to genetic, environmental, psychological and community factors. For the Aboriginal population more specifically, loss of culture, history of traumatic events, individual, family and community factors may also play a role in suicidal behaviour. Of particular concern is the high rate of suicide among Canadian Aboriginal youth. While the need to develop interventions to reduce suicidal behaviour for First Nations on-reserve populations is evident, there may be an element of distrust of researchers by Aboriginal communities. Furthermore, research in mental health and specifically suicide is much more sensitive than studying medical illnesses like diabetes. Clearly, this issue requires a unique and insightful approach. While numerous suicide prevention/intervention plans and guidelines have been published specifically for work involving Aboriginal people, the literature lacks a comprehensive discussion of the methodological and logistical issues faced by research teams and Aboriginal communities attempting to develop culturally-grounded and community-specific suicide prevention and intervention strategies. This paper outlines the research process, key challenges and lessons learned in a collaborative University-First Nations suicide prevention project conducted with eight north-western Manitoba First Nations communities (Canada)

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called episignatures ). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders

Community-based suicide prevention research in remote on-reserve first nations communities

Abstract Suicide is a complex problem linked to genetic, environmental, psychological and community factors. For the Aboriginal population more specifically, loss of culture, history of traumatic events, individual, family and community factors may also play a role in suicidal behaviour. Of particular concern is the high rate of suicide among Canadian Int J Ment Health Addiction (2010) Aboriginal youth. While the need to develop interventions to reduce suicidal behaviour for First Nations on-reserve populations is evident, there may be an element of distrust of researchers by Aboriginal communities. Furthermore, research in mental health and specifically suicide is much more sensitive than studying medical illnesses like diabetes. Clearly, this issue requires a unique and insightful approach. While numerous suicide prevention/intervention plans and guidelines have been published specifically for work involving Aboriginal people, the literature lacks a comprehensive discussion of the methodological and logistical issues faced by research teams and Aboriginal communities attempting to develop culturally-grounded and community-specific suicide prevention and intervention strategies. This paper outlines the research process, key challenges and lessons learned in a collaborative University-First Nations suicide prevention project conducted with eight north-western Manitoba First Nations communities (Canada)

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called “episignatures”). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders

Erratum: Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders (The American Journal of Human Genetics (2020) 106(3) (356–370), (S0002929720300197), (10.1016/j.ajhg.2020.01.019))

(The American Journal of Human Genetics 106, 356–370; March 5, 2020) In the version of this paper originally published, the underlying cause for Hunter McAlpine syndrome was incorrectly described in Table 1. The relevant description has been changed to read “Chr5q35-qter duplication involving NSD1” in the updated Table 1 reflected here. The authors apologize for this error