Aperçu: G.M.
Le
trouble du spectre de l'autisme est un trait complexe avec un haut
degré d'héritabilité ainsi qu'une susceptibilité par des
facteurs environnementaux.
L'étude n'a mis en évidence aucune
corrélation entre l'exposition moyenne à la pollution atmosphérique de
la conception à l'âge de 2 ans et le fardeau de la CNV (variation du nombre de copie) de l'enfant.
Il a été observé une
interaction significative dans laquelle une augmentation du taux de
duplication associé à une augmentation de 1SD de l'exposition à l'ozone
était associée à un risque élevé d'autisme beaucoup plus élevé que les risques accrus associés à la duplication
génomique ou de l'ozone seul.
Autism Res. 2017 Apr 27. doi: 10.1002/aur.1799.
The joint effect of air pollution exposure and copy number variation on risk for autism
Kim D1,2, Volk H3, Girirajan S1, Pendergrass S2, Hall MA1, Verma SS2, Schmidt RJ4,5, Hansen RL5,6, Ghosh D7, Ludena-Rodriguez Y4, Kim K, Ritchie MD1,2, Hertz-Picciotto I4,5, Selleck SB1.
Author information
- 1
- Department of Biochemistry & Molecular Biology, The Pennsylvania State University, University Park, PA, 16802.
- 2
- Biomedical & Translational Informatics Institute, Geisinger Health System, Danville, PA, 17822.
- 3
- Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205.
- 4
- Department of Public Health Sciences, University of California, Davis, Davis, CA.
- 5
- The MIND (Medical Investigation of Neurodevelopmental Disorders) Institute, University of California, Davis, Davis, CA.
- 6
- Department of Pediatrics, Davis School of Medicine, University of California, Sacramento, CA, 95817.
- 7
- Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045.
Abstract
Autism
spectrum disorder is a complex trait with a high degree of heritability
as well as documented susceptibility from environmental factors. In
this study the contributions of copy number variation, exposure to air
pollutants, and the interaction between the two on autism risk, were
evaluated in the population-based case-control Childhood Autism Risks
from Genetics and Environment (CHARGE) Study. For the current
investigation, we included only those CHARGE children (a) who met
criteria for autism or typical development and (b) for whom our team had
conducted both genetic evaluation of copy number burden and
determination of environmental air pollution exposures based on mapping
addresses from the pregnancy and early childhood. This sample consisted
of 158 cases of children with autism and 147 controls with typical
development. Multiple logistic regression models were fit with and
without environmental variable-copy number burden interactions. We found
no correlation between average air pollution exposure from conception
to age 2 years and the child's CNV burden. We found a significant
interaction in which a 1SD increase in duplication burden combined with a
1SD increase in ozone exposure was associated with an elevated autism
risk (OR 3.4, P < 0.005) much greater than the increased risks
associated with either genomic duplication (OR 1.85, 95% CI 1.25-2.73)
or ozone (OR 1.20, 95% CI 0.93-1.54) alone. Similar results were
obtained when CNV and ozone were dichotomized to compare those in the
top quartile relative to those having a smaller CNV burden and lower
exposure to ozone, and when exposures were assessed separately for
pregnancy, the first year of life, and the second year of life. No
interactions were observed for other air pollutants, even those that
demonstrated main effects; ozone tends to be negatively correlated with
the other pollutants examined. While earlier work has demonstrated
interactions between the presence of a pathogenic CNV and an
environmental exposure [Webb et al., 2016], these findings appear to be
the first indication that global copy number variation may increase
susceptibility to certain environmental factors, and underscore the need
to consider both genomics and environmental exposures as well as the
mechanisms by which each may amplify the risks for autism associated
with the other. Autism Res 2017. © 2017 International Society for Autism
Research, Wiley Periodicals, Inc.
© 2017 International Society for Autism Research, Wiley Periodicals, Inc.
- PMID: 28448694
- DOI: 10.1002/aur.1799
Aucun commentaire:
Enregistrer un commentaire