Emilie Théberge
Master of Science in Medical Genetics (MSc)
Research Topic
Investigating sex differences in the polygenic risk of major depressive disorder and shared associations with cardiovascular disease
Jessica Dennis
Assistant Professor
Research Classification
Research Interests
Administrative health data
Complex Trait Genetics
Electronic health records
Epidemiology
genetic epidemiology
Genetics of Neurological and Psychiatric Diseases
Machine Learning
Mental Health and Psychopathology in Children and Youth
Precision Health
statistical genetics
Relevant Degree Programs
Affiliations to Research Centres, Institutes & Clusters
Research Options
I am interested in and conduct interdisciplinary research.
Recruitment
Master's students
Doctoral students
Postdoctoral Fellows
Any time / year round
The last decade has seen an unprecedented explosion of data. In medicine, data are increasingly being generated and linked across electronic health records, administrative databases, and biobanked samples. These resources hold tremendous promise for improving human health and achieving precision medicine, which will only be realized by thoughtful study designs and innovative analyses.
My lab uses novel computational methods grounded in genetic epidemiology and statistical genetics to capitalize on today’s big data resources. We aim to understand how genetic and epigenetic differences between people contribute to variation in disease susceptibility, response to treatment, and recovery. A primary goal of our research is to reduce the suffering associated with psychiatric disorders, many of which first manifest in childhood and adolescence. We conduct studies in large population datasets, with a major interest in electronic health records and biobanks, and we work at the intersection of genetics, epidemiology, statistics, bioinformatics, and computer science.
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Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
Investigating sex differences in the polygenic risk of major depressive disorder and shared associations with cardiovascular disease (2022)
Major depressive disorder (MDD) is a leading cause of morbidity and disability worldwide, with approximately twice as many women reported to have a lifetime occurrence of MDD than men. MDD is a polygenic trait, wherein hundreds to thousands of common genetic variants with small effect sizes contribute to risk of disease. This study investigated sex differences in the risk factor comorbidity and genetic architecture of MDD in over 16,000 people aged 45-85 from the Canadian Longitudinal Study on Aging (CLSA), with 21% of females (n=1,741) and 12% of males (n=1,055) coded with MDD. Polygenic risk scores (PRS) for individuals were made using sex-stratified and non-sex-specific (“both-sexes”) UK Biobank genome-wide association study summary statistics data. The female sex-specific PRS had higher associations with MDD in females in the top decile of PRS risk (OR = 1.68 (1.32-2.14), p = 2.8E-05) than the male-specific PRS in males (OR = 1.43 (1.07-1.93), p = 0.017) and the both-sexes PRS applied to both sexes (OR = 1.51 (1.25-1.83), p = 2.5E-05). Odds of MDD for the sex-specific PRSs, socioeconomic, lifestyle and clinical risk factors were assessed using a multivariable logistic regression model for each sex. Sex-specific risk factor associations with odds of MDD were found in females (hypothyroidism (OR = 1.42 (1.25-1.63), p = 1.74E-07), not being partnered (OR = 1.34 (1.17-1.52), p = 1.26E-05), having diabetes (OR = 1.30 (1.11-1.52), p = 1.03E-03), higher sex-specific autosomal PRS (OR = 1.10 (1.04-1.16), p = 6.15E-04) and a history of ischemic heart disease (OR = 1.52 (1.14-2.01), p = 3.39E-03)) and males (high blood pressure, OR = 1.35 (1.04-1.47), p = 4.55E-05). Significant differences were observed in the proportion of variables that contributed to the most to each model, evaluated by relative pseudo-R2 values. Age contributed the most to the model for both sexes (73% for females, 57% for males), wherein younger age was associated with higher odds of MDD. The results of this thesis underscore the relevance for sex-disaggregating analyses of complex traits, like MDD, and the incorporation of clinical variables into models of MDD, in applications such as early detection and primary prevention.
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Publications
- Association of Preinjury Medical Diagnoses with Pediatric Persistent Postconcussion Symptoms in Electronic Health Records (2022)
Journal of Head Trauma Rehabilitation, 37 (2), E80-E89 - Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease. (2021)
Genome medicine, - Genetic risk for major depressive disorder and loneliness in sex-specific associations with coronary artery disease (2021)
Molecular Psychiatry, 26 (8), 4254-4264 - A phenome-wide association study identifying risk factors for pediatric post-concussion syndrome (2020)
medRxiv, - Lab-wide association scan of polygenic scores identifies biomarkers of complex disease (2020)
medRxiv, - A/T/N polygenic risk score for cognitive decline in old age (2019)
bioRxiv, - Diagnostic Algorithms to Study Post-Concussion Syndrome Using Electronic Health Records: Validating a Method to Capture an Important Patient Population. (2019)
Journal of neurotrauma, - Penetrance and pleiotropy of polygenic risk scores for schizophrenia in 106,160 patients across four health care systems (2019)
American Journal of Psychiatry, 176 (10), 846-855 - Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness (2019)
Human Molecular Genetics, 28 (22), 3853-3865 - Penetrance and pleiotropy of polygenic risk scores for schizophrenia in 106,160 patients across four healthcare systems (2018)
- Phenome-wide Investigation of Health Outcomes Associated with Genetic Predisposition to Loneliness (2018)
- Beyond the market? New agrarianism and cooperative farmland access in North America (2017)
Journal of Rural Studies, 53, 303--316 - Blood triglyceride levels are associated with DNA methylation at the serine metabolism gene PHGDH. (2017)
Scientific reports, - Blood triglyceride levels are associated with DNA methylation at the serine metabolism gene PHGDH. (2017)
Scientific reports, - Genetic determinants of tissue factor pathway inhibitor plasma levels (2017)
Thrombosis and Haemostasis, 114 (08), 245--257 - Leveraging cell type specific regulatory regions to detect SNPs associated with tissue factor pathway inhibitor plasma levels. (2017)
Genetic epidemiology, - Leveraging cell type specific regulatory regions to detect SNPs associated with tissue factor pathway inhibitor plasma levels. (2017)
Genetic epidemiology, - Bicycling crashes on streetcar (tram) or train tracks: mixed methods to identify prevention measures. (2016)
BMC public health, - Bicycling crashes on streetcar (tram) or train tracks: mixed methods to identify prevention measures. (2016)
BMC public health, - Single nucleotide polymorphisms in an intergenic chromosome 2q region associated with tissue factor pathway inhibitor plasma levels and venous thromboembolism (2016)
Journal of Thrombosis and Haemostasis, 14 (10), 1960--1970 - Single nucleotide polymorphisms in an intergenic chromosome 2q region associated with tissue factor pathway inhibitor plasma levels and venous thromboembolism. (2016)
Journal of thrombosis and haemostasis : JTH, - Bicycling injury hospitalisation rates in Canadian jurisdictions: analyses examining associations with helmet legislation and mode share. (2015)
BMJ open, - Genome-wide investigation of DNA methylation marks associated with FV Leiden mutation. (2014)
PloS one, - RFC1 80G>A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: a human genome epidemiologic review and meta-analysis of observational studies. (2014)
Arthritis & rheumatology (Hoboken, N.J.), - Thrombin generation potential and whole-blood DNA methylation. (2014)
Thrombosis research, - Challenges of population-based colorectal cancer screening and the importance of time-trend analysis when evaluating system change. (2013)
Cancer epidemiology, - Helmet legislation and admissions to hospital for cycling related head injuries in Canadian provinces and territories: interrupted time series analysis. (2013)
The BMJ, - The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies. (2012)
Blood, - Bias in the case-only design applied to studies of gene-environment and gene-gene interaction: a systematic review and meta-analysis. (2011)
International journal of epidemiology, - Breast cancer risk in relation to alcohol consumption and BRCA gene mutations--a case-only study of gene-environment interaction. (2011)
The breast journal, - Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers. (2010)
Breast (Edinburgh, Scotland), - The effects of provincial bicycle helmet legislation on helmet use and bicycle ridership in Canada. (2010)
Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,
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BC Children's Hospital
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