- Overview
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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.
- Publications
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Sex-dependent placental methylation quantitative trait loci provide insight into the prenatal origins of childhood onset traits and conditions
iScience
William Casazza and Amy M. Inkster and Giulia F. Del Gobbo and Victor Yuan and Fabien Delahaye and Carmen Marsit and Yongjin P. Park and Wendy P. Robinson and Sara Mostafavi and Jessica K. Dennis
DOI: 10.1016/j.isci.2024.109047
02/2024Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)
Emilie Théberge and Jessica Dennis
DOI: 10.1101/2023.04.10.23288267
04/2023Sex-dependent placental mQTL provide insight into the prenatal origins of childhood-onset traits and conditions
William Casazza and Amy M. Inkster and Giulia F. Del Gobbo and Victor Yuan and Fabien Delahaye and Carmen Marsit and Yongjin P. Park and Wendy P. Robinson and Sara Mostafavi and Jessica K Dennis
DOI: 10.1101/2022.10.04.22280695
10/2022Usage of biobank data for psychiatric genomics and promotion of precision psychiatry
Psychiatric Genomics
Davis, L.K. and Kiri Dennis, J.
DOI: 10.1016/B978-0-12-819602-1.00018-8
2022Association of Preinjury Medical Diagnoses with Pediatric Persistent Postconcussion Symptoms in Electronic Health Records
Journal of Head Trauma Rehabilitation
Yengo-Kahn, A.M. and Hibshman, N. and Bonfield, C.M. and Torstenson, E.S. and Gifford, K.A. and Belikau, D. and Davis, L.K. and Zuckerman, S.L. and Dennis, J.K.
DOI: 10.1097/HTR.0000000000000686
2022Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease.
Genome medicine
Dennis JK and Sealock JM and Straub P and Lee YH and Hucks D and Actkins K and Faucon A and Feng YA and Ge T and Goleva SB and Niarchou M and Singh K and Morley T and Smoller JW and Davis LK
DOI: 10.1186/s13073-020-00820-8
PubMed: 33441150
01/2021Genetic risk for major depressive disorder and loneliness in sex-specific associations with coronary artery disease
Molecular Psychiatry
Dennis, J. and Sealock, J. and Levinson, R.T. and Farber-Eger, E. and Franco, J. and Fong, S. and Straub, P. and Hucks, D. and Song, W.-L. and Linton, M.R.F. and Fontanillas, P. and Elson, S.L. and Ruderfer, D. and Abdellaoui, A. and Sanchez-Roige, S. and Palmer, A.A. and Boomsma, D.I. and Cox, N.J. and Chen, G. and Mosley, J.D. and Wells, Q.S. and Davis, L.K.
DOI: 10.1038/s41380-019-0614-y
2021A phenome-wide association study identifying risk factors for pediatric post-concussion syndrome
Aaron M. Yengo-Kahn and Natalie Hibshman and Christopher M. Bonfield and Eric S. Torstenson and Katherine A. Gifford and Daniil Belikau and Lea K. Davis and Scott L. Zuckerman and Jessica K. Dennis
DOI: 10.1101/2020.07.17.20155895
07/2020Lab-wide association scan of polygenic scores identifies biomarkers of complex disease
medRxiv
Dennis, J.K. and Sealock, J.M. and Straub, P. and Hucks, D. and Actkins, K. and Faucon, A. and Goleva, S.B. and Nirachou, M. and Singh, K. and Morley, T. and Ruderfer, D.M. and Mosley, J.D. and Chen, G. and Davis, L.K.
DOI: 10.1101/2020.01.24.20018713
2020A/T/N polygenic risk score for cognitive decline in old age
bioRxiv
Moore, A.M. and Filshtein, T.J. and Dumitrescu, L. and Harrati, A. and Elahi, F. and Mormino, E.C. and Deming, Y. and Kunkle, B.W. and Mungas, D.M. and Hedden, T. and Apostolova, L.G. and Saykin, A.J. and Chasioti, D. and Lu, Q. and Dennis, J. and Sealock, J. and Davis, L.K. and Fardo, D.W. and Buckley, R. and Hohman, T.J.
DOI: 10.1101/838847
2019Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness
Human Molecular Genetics
Abdellaoui, A. and Sanchez-Roige, S. and Sealock, J. and Treur, J.L. and Dennis, J. and Fontanillas, P. and Elson, S. and Nivard, M.G. and Ip, H.F. and Van Der Zee, M. and Baselmans, B.M.L. and Hottenga, J.J. and Willemsen, G. and Mosing, M. and Lu, Y. and Pedersen, N.L. and Denys, D. and Amin, N. and M Van Duijn, C. and Szilagyi, I. and Tiemeier, H. and Neumann, A. and Verweij, K.J.H. and Cacioppo, S. and Cacioppo, J.T. and Davis, L.K. and Palmer, A.A. and Boomsma, D.I.
DOI: 10.1093/hmg/ddz219
2019Penetrance and pleiotropy of polygenic risk scores for schizophrenia in 106,160 patients across four health care systems
American Journal of Psychiatry
Zheutlin, A.B. and Dennis, J. and Linnér, R.K. and Moscati, A. and Restrepo, N. and Straub, P. and Ruderfer, D. and Castro, V.M. and Chen, C.-Y. and Ge, T. and Huckins, L.M. and Charney, A. and Kirchner, H.L. and Stahl, E.A. and Chabris, C.F. and Davis, L.K. and Smoller, J.W.
DOI: 10.1176/appi.ajp.2019.18091085
2019Diagnostic algorithms to study post-concussion syndrome using electronic health records: Validating a method to capture an important patient population
Journal of Neurotrauma
Dennis, J. and Yengo-Kahn, A.M. and Kirby, P. and Solomon, G.S. and Cox, N.J. and Zuckerman, S.L.
DOI: 10.1089/neu.2018.5916
2019Penetrance and pleiotropy of polygenic risk scores for schizophrenia in 106,160 patients across four healthcare systems
Zheutlin AB and Dennis J and Linnér RK and Moscati A and Restrepo N and Straub P and Ruderfer D and Castro VM and Chen C and Ge T and Huckins LM and Charney A and Lester Kirchner H and Smoller JW
DOI: 10.1101/421164
09/2018Beyond the market? New agrarianism and cooperative farmland access in North America
Journal of Rural Studies
Hannah Wittman and Jessica Dennis and Heather Pritchard
DOI: 10.1016/j.jrurstud.2017.03.007
07/2017Leveraging cell type specific regulatory regions to detect SNPs associated with tissue factor pathway inhibitor plasma levels
Genetic Epidemiology
Dennis, J. and Medina-Rivera, A. and Truong, V. and Antounians, L. and Zwingerman, N. and Carrasco, G. and Strug, L. and Wells, P. and Trégouët, D.-A. and Morange, P.-E. and Wilson, M.D. and Gagnon, F.
DOI: 10.1002/gepi.22049
2017Blood triglyceride levels are associated with DNA methylation at the serine metabolism gene PHGDH
Scientific Reports
Truong, V. and Huang, S. and Dennis, J. and Lemire, M. and Zwingerman, N. and Aïssi, D. and Kassam, I. and Perret, C. and Wells, P. and Morange, P.-E. and Wilson, M. and Trégouët, D.-A. and Gagnon, F.
DOI: 10.1038/s41598-017-09552-z
2017Bicycling crashes on streetcar (tram) or train tracks: Mixed methods to identify prevention measures
BMC Public Health
Teschke, K. and Dennis, J. and Reynolds, C.C.O. and Winters, M. and Harris, M.A.
DOI: 10.1186/s12889-016-3242-3
2016Single nucleotide polymorphisms in an intergenic chromosome 2q region associated with tissue factor pathway inhibitor plasma levels and venous thromboembolism
Journal of Thrombosis and Haemostasis
Dennis, J. and Truong, V. and Aïssi, D. and Medina-Rivera, A. and Blankenberg, S. and Germain, M. and Lemire, M. and Antounians, L. and Civelek, M. and Schnabel, R. and Wells, P. and Wilson, M.D. and Morange, P.-E. and Trégouët, D.-A. and Gagnon, F.
DOI: 10.1111/jth.13431
2016Bicycling injury hospitalisation rates in Canadian jurisdictions: Analyses examining associations with helmet legislation and mode share
BMJ Open
Teschke, K. and Koehoorn, M. and Shen, H. and Dennis, J.
DOI: 10.1136/bmjopen-2015-008052
2015Genetic determinants of tissue factor pathway inhibitor plasma levels
Thrombosis and Haemostasis
Dennis, J. and Kassam, I. and Morange, P.-E. and Trégouët, D.-A. and Gagnon, F.
DOI: 10.1160/TH14-12-1043
2015Thrombin generation potential and whole-blood DNA methylation
Thrombosis Research
Rocañín-Arjó, A. and Dennis, J. and Suchon, P. and Aïssi, D. and Truong, V. and Trégouët, D.-A. and Gagnon, F. and Morange, P.-E.
DOI: 10.1016/j.thromres.2014.12.010
2015RFC1 80G>A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: A human genome epidemiologic review and meta-analysis of observational studies
Arthritis and Rheumatology
Kung, T.N. and Dennis, J. and Ma, Y. and Xie, G. and Bykerk, V. and Pope, J. and Thorne, C. and Keystone, E. and Siminovitch, K.A. and Gagnon, F.
DOI: 10.1002/art.38331
2014Genome-Wide investigation of DNA methylation marks associated with FV Leiden mutation
PLoS ONE
Aïssi, D. and Dennis, J. and Ladouceur, M. and Truong, V. and Zwingerman, N. and Rocanin-Arjo, A. and Germain, M. and Paton, T.A. and Morange, P.-E. and Gagnon, F. and Trégouë, D.-A.
DOI: 10.1371/journal.pone.0108087
2014Challenges of population-based colorectal cancer screening and the importance of time-trend analysis when evaluating system change
Cancer Epidemiology
Zarychanski, R. and Dennis, J. and Singh, H.
DOI: 10.1016/j.canep.2013.10.007
2013Helmet legislation and admissions to hospital for cycling related head injuries in Canadian provinces and territories: Interrupted time series analysis
BMJ (Online)
Dennis, J. and Ramsay, T. and Turgeon, A.F. and Zarychanski, R.
DOI: 10.1136/bmj.f2674
2013The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: A HuGE review and meta-analysis of evidence from observational studies
Blood
Dennis, J. and Johnson, C.Y. and Adediran, A.S. and De Andrade, M. and Heit, J.A. and Morange, P.-E. and Trégouët, D.-A. and Gagnon, F.
DOI: 10.1182/blood-2011-10-383448
2012Breast cancer risk in relation to alcohol consumption and BRCA gene mutations - A case-only study of gene-environment interaction
Breast Journal
Dennis, J. and Krewski, D. and Côté, F.-S. and Fafard, E. and Little, J. and Ghadirian, P.
DOI: 10.1111/j.1524-4741.2011.01133.x
2011Bias in the case-only design applied to studies of gene-environment and gene-gene interaction: A systematic review and meta-analysis
International Journal of Epidemiology
Dennis, J. and Hawken, S. and Krewski, D. and Birkett, N. and Gheorghe, M. and Frei, J. and McKeown-Eyssen, G. and Little, J.
DOI: 10.1093/ije/dyr088
2011The effects of provincial bicycle helmet legislation on helmet use and bicycle ridership in canada
Injury Prevention
Dennis, J. and Potter, B. and Ramsay, T. and Zarychanski, R.
DOI: 10.1136/ip.2009.025353
2010Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers
Breast
Dennis, J. and Ghadirian, P. and Little, J. and Lubinski, J. and Gronwald, J. and Kim-Sing, C. and Foulkes, W. and Moller, P. and Lynch, H.T. and Neuhausen, S.L. and Domchek, S. and Armel, S. and Isaacs, C. and Tung, N. and Sweet, K. and Ainsworth, P. and Sun, P. and Krewski, D. and Narod, S.
DOI: 10.1016/j.breast.2010.05.009
2010Genetic risk for major depressive disorder and loneliness in gender-specific associations with coronary artery disease: supplementary
Jessica Dennis and Julia Sealock and Rebecca T Levinson and Eric Farber-Eger and Jacob Franco and Sarah Fong and Peter Straub and Donald Hucks and MacRae F Linton and Wen-Liang Song and Pierre Fontanillas and Sarah L Elson and Douglas Ruderfer and Abdel Abdellaoui and Sandra Sanchez-Roige and Abraham A Palmer and Dorret I Boomsma and Nancy Cox and Guanhua Chen and Jonathan D Mosley and Quinn S Wells and Lea Davis
DOI: 10.1101/512541 - Research
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Genetics of Brain-Related Disorders
Brain-related disorders such as depression and Alzheimer’s disease account for more years of life lost to disability and death than either cancer or cardiovascular disease. Three quarters of psychiatric disorders manifest in childhood and adolescence, and brain-related disorders affect not only the person with the disorder, but also their family and support systems as well. Our research is directed towards reducing the suffering associated with psychiatric and neurological disorders by understanding genetic influences on these traits.
We have studied genetic risk factors for loneliness, depression, and schizophrenia in large consortia, including the PsycheMERGE consortium. PsycheMERGE is a growing network of clinical sites with electronic health records linked to genomic data, which we leverage for psychiatric genetics research.
We also have ongoing projects on the role of genetics in traumatic brain injury recovery. Concussions are sustained by one in 150 Canadians each year. In the short term, people with concussions may struggle to resume pre-injury activities months after the injury. In the long term, concussions have been linked to dementia and Alzheimer’s disease. We are looking for genetic risk profiles that help us identify people at risk of poor recovery soon after their injury, so that we can provide treatment before these bad outcomes arise.Harnessing “Big Data” to Advance Precision Health
Data collected in routine clinical care are a huge source of potentially valuable data. These data include electronic health records (EHRs) and other health administrative records, such as information on prescriptions filled and laboratory test results. The Dennis lab analyzes these data using advanced computational approaches in order to advance precision health. We apply machine learning techniques to clinical data so that we can identify data-driven patient groupings. These groupings often reveal disease patterns that we didn’t know existed. In this way, we’re moving beyond a one-size-fits all disease classification system, towards one that’s more tailored to each person’s individual data.
Clinical data linked to other large genomic and environmental datasets are also leading to advances in precision health. We are applying statistical genetics methods for the prediction and early detection of brain-related disorders in the US-based PsycheMERGE consortium. In Canada, we are moving towards similar approaches. BC Children’s Hospital has prioritized digital health research, which aims to harness data and technologies to improve health outcomes. The Dennis lab is on the forefront of these digital health innovations. We will play a key role in developing data resources combining clinical, genomic, and environmental data, to advance patient-centered, precision health in Canada.Genomic Data Integration
New technologies are allowing us to query the human body like never before. We can now measure genetic variation across the whole genome, and relate it to gene expression and epigenetic marks in multiple cells and tissues. These measurements have revealed that the interactions between molecules in our bodies are hugely complex and dynamic, changing over time and in response to different environments.
Studying the relationships between different genomic molecules (such as genes expressed and epigenetic marks) will help us understand the basis of health and disease. The Dennis lab uses computational methods that integrate different datasets to learn about disease processes. For example, collaborators studying gene regulation recently discovered that some genomic regions were more versatile than we previously thought, specifically, that some gene promoters could double as gene enhancers. We are now are exploring how mutations in these genomic regions impact human health and disease susceptibility by integrating data on gene regulation with data on human health in large biobank datasets.Research Group MembersPaola Arguello, Graduate Research Assistant
Emily Barr, PhD Student
Sabine Bonnor, INSPIRE Student
Graham Boucher, Data Analyst, Data Analyst
Christine Chen, Graduate Student
Maude Comtois-Cabana, PhD candidate
Jasmin Lee, Graduate Student
Karanvir Singh
Using Big Data to Personalize Medicine: Q&A with Dr. Jessica Dennis
Dr. Jessica Dennis is working to harness big data to enable personalized medicine. She’s using large population health datasets to discover how a person’s genes and environment can affect their likelihood of developing disease, their response to treatment and ultimately, their recovery.
