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Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders

Brennan H. Baker, Shaoyi Zhang, Jeremy M. Simon, Sarah M. McLarnan, Wendy K. Chung, Brandon L. Pearson
doi: https://doi.org/10.1101/2021.12.17.473207
Brennan H. Baker
1Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
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Shaoyi Zhang
2Master of Public Health Program, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032
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Jeremy M. Simon
3Department of Genetics and Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
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Sarah M. McLarnan
1Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
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Wendy K. Chung
4Departments of Pediatrics and Medicine, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032
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Brandon L. Pearson
1Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
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  • For correspondence: blp2125@cumc.columbia.edu
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Abstract

De novo mutations contribute to a large proportion of sporadic psychiatric and developmental disorders, yet the potential role of environmental carcinogens as drivers of causal de novo mutations in neurodevelopmental disorders is poorly studied. We demonstrate that several mutagens, including polycyclic aromatic hydrocarbons (PAHs), disproportionately mutate genes related to neurodevelopmental disorders including autism spectrum disorders (ASD), schizophrenia, and attention deficit hyperactivity disorder (ADHD). Other disease genes including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, congenital heart disease, orofacial clefts, and coronary artery disease were generally not mutated more than expected. Our findings support a new paradigm of neurodevelopmental disease etiology driven by a contribution of environmentally induced rather than random mutations.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 20, 2021.
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Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders
Brennan H. Baker, Shaoyi Zhang, Jeremy M. Simon, Sarah M. McLarnan, Wendy K. Chung, Brandon L. Pearson
bioRxiv 2021.12.17.473207; doi: https://doi.org/10.1101/2021.12.17.473207
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Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders
Brennan H. Baker, Shaoyi Zhang, Jeremy M. Simon, Sarah M. McLarnan, Wendy K. Chung, Brandon L. Pearson
bioRxiv 2021.12.17.473207; doi: https://doi.org/10.1101/2021.12.17.473207

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