Jon Krohn
DPhil student

Contact details
Email: jon.krohn@magd.ox.ac.uk
Tel: 01865 287680
Research summary:
Broadly, I'm interested in the many factors - genetic and environmental - that tend to lead to disease. For my doctorate, I'm focusing on investigating clinical anxiety and unipolar depression, because of the high prevalance of these diseases, their massive impact on an individual's quality of life, and how poorly understood they are at present. It is synergistic to study anxiety and depression simultaneously because they have many overlapping risk factors, symptoms and treatments. Not surprisingly given these similarities, anxiety and depression also frequently co-occur in an individual.
The vast majority of my doctoral research is computational. I apply a variety of statistical techniques to large data sets (such as those derived from heterogeneous stock mice) in attempts to find reliable relationships between disease-related traits and their many potential risk factors, including genetic markers, gene expression data and environmental variables. Once these relationships are established, I employ algorithms intended to identify the causal pathways by which these factors are related. For example, a particular genetic sequence may affect the extent to which a gene is expressed in the central nervous system, which in turn may influence an individual's susceptibility to anxiety and depression. Once potential causal pathways are determined in this way, experiments (e.g., gene knockout, conditional transgenic) can subsequently be carried out to verify their validity.
Ultimately, understanding the biological pathways underlying disease could lead to the identification of therapeutic drug targets, while recognition of the aspects of an individual's environment that contribute to the disease can inform preventative measures. In the case of anxiety and depression, this translates to improved quality of life for those who are afflicted.
Publications list:
2013:
- Sex-stratified genome-wide association studies in 270,000 individuals show evidence for sexual dimorphism in genetic loci for anthropometric traits. Randall JC, Winkler TW, Kutalik Z, Berndt SI, Jackson AU, et al. PLoS Genetics (in press)
2011:
- Biomarker validation and QTL fine mapping using sparse instrumental variables. Agakov F, Colombo M, Krohn J, Flint J, McKeigue P. (submitted)
- Sparse Instrumental Variables: an integrative approach to biomarker validation. Agakov F, Krohn J, Colombo M, McKeigue P. Journal of Epidemiology and Community Health 65: A10
- A comparison of exogenous promoter activity at the ROSA26 locus using a PhiC31 integrase mediated cassette exchange approach in mouse ES cells. Chen C-M, Krohn J, Bhattacharya S, Davies B. PLoS ONE 6(8): e23376
- Inference of causal relationships between biomarkers and outcomes in high dimensions. Agakov F, McKeigue P, Krohn J, Flint J. Journal of Systemics, Cybernetics and Informatics 9: 1-8
- Association of UV radiation with multiple sclerosis prevalence and sex ratio in France. Orton S, Wald L, Confavreux C, Vukusic S, Krohn J, Ramagopalan S, Herrera B, Sadovnick A, Ebers G. Neurology 76: 425-31
2010:
- Inference of causal relationships between biomarkers and outcomes in high dimensions. Agakov F, McKeigue P, Krohn J, Flint J. Proceedings of the Fourth International Symposium on Bio- and Medical Informatics and Cybernetics (selected as top paper from amongst seven in its category)
- Sparse Instrumental Variables (SPIV) for genome-wide studies. Agakov F, McKeigue P, Krohn J, Storkey A. Advances in Neural Information Processing Systems 23 (Edited by: J Lafferty, C Williams, J Shawe-Taylor, R Zemel & A Culotta)
2008:
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Exposure to a context previously associated with nausea elicits conditioned gaping in rats: A model of anticipatory nausea. Limebeer CL, Krohn JP, Cross-Mellor S, Litt DE, Ossenkopp K-P, Parker LA. Behav Brain Res 187: 33-40
Presentations:
2011:
- Fine-Mapping QTL and Inferring Causal Pathways that Underlie Sixty Murine Phenotypes. Mouse Genetics conference in Washington, D.C. (selected as "Outstanding Student Presentation" from a field of sixteen students)
2010:
- Gene-by-Environment Interactions Underlying Anxiety Across Six Murine Experiments. Complex Trait Community conference at Northwestern University in Chicago
- Sex-by-Gene Interactions in 100 Murine Phenotypes Investigated by Resample Model Averaging. European Mathematical Genetics Meeting at the University of Oxford
Seminar Chair:
2010:
- Early-onset mood and anxiety problems: the role of early life adversities, epigenetic mechanisms and continuing brain development. Magdalen College, University of Oxford
Research areas:
Neuroscience, genetics
Keywords:
Neuroscience, genetics, anxiety, depression, fear-related behaviour, gene expression, DNA, RNA, causal pathway.


