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The interaction of ozone and copy number variation on risk for autism: Does environmental exposure to nitrous oxide explain the interaction?

The interaction of ozone and copy number variation on risk for autism: Does environmental... Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders, and although the spectrum is thought to be heritable, no single gene has been identified that can adequately explain the disorder's complex heterogeneity and increasing prevalence. Kim et al. [] utilized population‐based case‐control CHARGE Study to investigate the influence of copy number variation, exposure to air pollutants, and the interaction between the two on the risk of ASD. The authors reported their main finding that a 1SD increase in duplication burden interacted with a 1SD increase in ozone exposure to significantly increase ASD risk, an increase much greater than the risk posed by either exposure alone.In Table 1, the OR for interaction between ozone and duplication or total CNV burden is smaller than the OR for the main CNV burden effect. As a main effect, ozone showed the lowest odds for ASD among all pollutants studied. Figure 1 shows a greater number of quartiles in the low ozone area with a higher proportion of individuals with ASD, but this cluster appears to be overlooked in the interpretation. These data argue that ozone exposure could be protective against ASD. We have recently postulated that exposure to the pervasive agricultural and combustion pollutant, nitrous oxide (N2O), may underlie the increasing prevalence of neurodevelopmental disorders [Fluegge, and My Bibliography @ PubMed: https://www.ncbi.nlm.nih.gov/sites/myncbi/1r5h3UjOlyj5q/bibliography/51230181/public/?sort=date&direction=descending]. Our review of this novel hypothesis highlighted pathophysiological mechanisms of action including glutamatergic (NMDA receptor) and cholinergic (α7 nicotinic acetylcholine receptor) antagonism, stimulation of dynorphin release and kappa opioid receptor activation, a class of opioid peptides that has been implicated in ASD traits including behavioral stereotypy, socio‐communicative deficits, and gait abnormality [Fluegge, ].Related to the gene–pollutant interaction suggested by Kim et al. [], N2O is the primary agent of ozone depletion [Ravishankara, Daniel, & Portmann, ]. Plant breeding studies provide evidence that chromosomal doubling—a rare natural phenomenon in haploid plants—can be induced from N2O exposure [Kato & Geiger, ]. In areas where elevated ozone necessitates greater use of anthropogenic nitrogen to rescue ozone‐depleted agricultural growth and yield [Bhatia et al., ; Broberg et al., ], greater N2O emissions could increase offspring CNV burden, thus creating the false‐positive interaction between ozone and CNV in ASD risk. We believe N2O should be considered in any CNV–ozone interaction for its influence in ozone stasis as well as its putative benefit in plant breeding due to enhanced chromosomal duplication.ReferencesBhatia, A., Ghosh, A., Kumar, V., Tomer, R., Singh, S.D., & Pathak, H. (2011). Effect of elevated tropospheric ozone on methane and nitrous oxide emission from rice soil in north India. Agriculture, Ecosystems & Environment, 144, 21–28. doi:10.1016/j.agee.2011.07.003Broberg, M. C., Uddling, J., Mills, G., Pleijel, H. (2017). Fertilizer efficiency in wheat is reduced by ozone pollution. The Science of the Total Environment, 607–608, 876–880. doi: 10.1016/j.scitotenv.2017.07.069.Fluegge, K. (2016). Does environmental exposure to the greenhouse gas, N2O, contribute to etiological factors in neurodevelopmental disorders? A mini‐review of the evidence. Environmental Toxicology and Pharmacology, 47, 6–18. doi: 10.1016/j.etap.2016.08.013Kato, A., & Geiger, H.H. (2002). Chromosome doubling of haploid maize seedlings using nitrous oxide gas at the flower primordial stage. Plant Breeding, 121, 370–377. doi: 10.1046/j.1439-0523.2002.743321.xKim, D., Volk, H., Girirajan, S., Pendergrass, S., Hall, M.A., Verma, S.S., … Selleck S.B. (2017). The joint effect of air pollution exposure and copy number variation on risk for autism. Autism Research, 10, 1470–1480. doi: 10.1002/aur.1799.Ravishankara, A.R., Daniel, J.S., & Portmann, R.W. (2009). Nitrous oxide (N2O): the dominant ozone‐depleting substance emitted in the 21st century. Science, 326, 123–125. doi:10.1126/science.1176985 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Autism Research Wiley

The interaction of ozone and copy number variation on risk for autism: Does environmental exposure to nitrous oxide explain the interaction?

Fluegge, Keith
Autism Research , Volume 11 (4) – Jan 1, 2018
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References (7)

Publisher
Wiley
Copyright
© 2018 International Society for Autism Research, Wiley Periodicals, Inc.
ISSN
1939-3792
eISSN
1939-3806
DOI
10.1002/aur.1944
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Abstract

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders, and although the spectrum is thought to be heritable, no single gene has been identified that can adequately explain the disorder's complex heterogeneity and increasing prevalence. Kim et al. [] utilized population‐based case‐control CHARGE Study to investigate the influence of copy number variation, exposure to air pollutants, and the interaction between the two on the risk of ASD. The authors reported their main finding that a 1SD increase in duplication burden interacted with a 1SD increase in ozone exposure to significantly increase ASD risk, an increase much greater than the risk posed by either exposure alone.In Table 1, the OR for interaction between ozone and duplication or total CNV burden is smaller than the OR for the main CNV burden effect. As a main effect, ozone showed the lowest odds for ASD among all pollutants studied. Figure 1 shows a greater number of quartiles in the low ozone area with a higher proportion of individuals with ASD, but this cluster appears to be overlooked in the interpretation. These data argue that ozone exposure could be protective against ASD. We have recently postulated that exposure to the pervasive agricultural and combustion pollutant, nitrous oxide (N2O), may underlie the increasing prevalence of neurodevelopmental disorders [Fluegge, and My Bibliography @ PubMed: https://www.ncbi.nlm.nih.gov/sites/myncbi/1r5h3UjOlyj5q/bibliography/51230181/public/?sort=date&direction=descending]. Our review of this novel hypothesis highlighted pathophysiological mechanisms of action including glutamatergic (NMDA receptor) and cholinergic (α7 nicotinic acetylcholine receptor) antagonism, stimulation of dynorphin release and kappa opioid receptor activation, a class of opioid peptides that has been implicated in ASD traits including behavioral stereotypy, socio‐communicative deficits, and gait abnormality [Fluegge, ].Related to the gene–pollutant interaction suggested by Kim et al. [], N2O is the primary agent of ozone depletion [Ravishankara, Daniel, & Portmann, ]. Plant breeding studies provide evidence that chromosomal doubling—a rare natural phenomenon in haploid plants—can be induced from N2O exposure [Kato & Geiger, ]. In areas where elevated ozone necessitates greater use of anthropogenic nitrogen to rescue ozone‐depleted agricultural growth and yield [Bhatia et al., ; Broberg et al., ], greater N2O emissions could increase offspring CNV burden, thus creating the false‐positive interaction between ozone and CNV in ASD risk. We believe N2O should be considered in any CNV–ozone interaction for its influence in ozone stasis as well as its putative benefit in plant breeding due to enhanced chromosomal duplication.ReferencesBhatia, A., Ghosh, A., Kumar, V., Tomer, R., Singh, S.D., & Pathak, H. (2011). Effect of elevated tropospheric ozone on methane and nitrous oxide emission from rice soil in north India. Agriculture, Ecosystems & Environment, 144, 21–28. doi:10.1016/j.agee.2011.07.003Broberg, M. C., Uddling, J., Mills, G., Pleijel, H. (2017). Fertilizer efficiency in wheat is reduced by ozone pollution. The Science of the Total Environment, 607–608, 876–880. doi: 10.1016/j.scitotenv.2017.07.069.Fluegge, K. (2016). Does environmental exposure to the greenhouse gas, N2O, contribute to etiological factors in neurodevelopmental disorders? A mini‐review of the evidence. Environmental Toxicology and Pharmacology, 47, 6–18. doi: 10.1016/j.etap.2016.08.013Kato, A., & Geiger, H.H. (2002). Chromosome doubling of haploid maize seedlings using nitrous oxide gas at the flower primordial stage. Plant Breeding, 121, 370–377. doi: 10.1046/j.1439-0523.2002.743321.xKim, D., Volk, H., Girirajan, S., Pendergrass, S., Hall, M.A., Verma, S.S., … Selleck S.B. (2017). The joint effect of air pollution exposure and copy number variation on risk for autism. Autism Research, 10, 1470–1480. doi: 10.1002/aur.1799.Ravishankara, A.R., Daniel, J.S., & Portmann, R.W. (2009). Nitrous oxide (N2O): the dominant ozone‐depleting substance emitted in the 21st century. Science, 326, 123–125. doi:10.1126/science.1176985

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Autism Research – Wiley

Published: Jan 1, 2018

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