The joint effect of air pollution exposure and copy number variation on risk for autism

Dokyoon Kim, Heather Volk, Santhosh Girirajan, Sarah Pendergrass, Molly Hall, Shefali S. Verma, Rebecca J. Schmidt, Robin L. Hansen, Debashis Ghosh, Yunin Ludena-Rodriguez, Kyoungmi Kim, Marylyn Deriggi Ritchie, Irva Hertz-Picciotto, Scott Brian Selleck

Research output: Contribution to journalArticle

6 Citations (Scopus)

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, 10: 1470–1480.

Original languageEnglish (US)
Pages (from-to)1470-1480
Number of pages11
JournalAutism Research
Volume10
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Air Pollution
Autistic Disorder
Ozone
Air Pollutants
Environmental Exposure
Logistic Models
Pregnancy
Environmental Pollution
Genomics
Population

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)

Cite this

Kim, Dokyoon ; Volk, Heather ; Girirajan, Santhosh ; Pendergrass, Sarah ; Hall, Molly ; Verma, Shefali S. ; Schmidt, Rebecca J. ; Hansen, Robin L. ; Ghosh, Debashis ; Ludena-Rodriguez, Yunin ; Kim, Kyoungmi ; Ritchie, Marylyn Deriggi ; Hertz-Picciotto, Irva ; Selleck, Scott Brian. / The joint effect of air pollution exposure and copy number variation on risk for autism. In: Autism Research. 2017 ; Vol. 10, No. 9. pp. 1470-1480.
@article{b694cba48fe54131b9fc4fe112f937db,
title = "The joint effect of air pollution exposure and copy number variation on risk for autism",
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, 10: 1470–1480.",
author = "Dokyoon Kim and Heather Volk and Santhosh Girirajan and Sarah Pendergrass and Molly Hall and Verma, {Shefali S.} and Schmidt, {Rebecca J.} and Hansen, {Robin L.} and Debashis Ghosh and Yunin Ludena-Rodriguez and Kyoungmi Kim and Ritchie, {Marylyn Deriggi} and Irva Hertz-Picciotto and Selleck, {Scott Brian}",
year = "2017",
month = "9",
day = "1",
doi = "10.1002/aur.1799",
language = "English (US)",
volume = "10",
pages = "1470--1480",
journal = "Autism Research",
issn = "1939-3806",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

Kim, D, Volk, H, Girirajan, S, Pendergrass, S, Hall, M, Verma, SS, Schmidt, RJ, Hansen, RL, Ghosh, D, Ludena-Rodriguez, Y, Kim, K, Ritchie, MD, Hertz-Picciotto, I & Selleck, SB 2017, 'The joint effect of air pollution exposure and copy number variation on risk for autism', Autism Research, vol. 10, no. 9, pp. 1470-1480. https://doi.org/10.1002/aur.1799

The joint effect of air pollution exposure and copy number variation on risk for autism. / Kim, Dokyoon; Volk, Heather; Girirajan, Santhosh; Pendergrass, Sarah; Hall, Molly; Verma, Shefali S.; Schmidt, Rebecca J.; Hansen, Robin L.; Ghosh, Debashis; Ludena-Rodriguez, Yunin; Kim, Kyoungmi; Ritchie, Marylyn Deriggi; Hertz-Picciotto, Irva; Selleck, Scott Brian.

In: Autism Research, Vol. 10, No. 9, 01.09.2017, p. 1470-1480.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The joint effect of air pollution exposure and copy number variation on risk for autism

AU - Kim, Dokyoon

AU - Volk, Heather

AU - Girirajan, Santhosh

AU - Pendergrass, Sarah

AU - Hall, Molly

AU - Verma, Shefali S.

AU - Schmidt, Rebecca J.

AU - Hansen, Robin L.

AU - Ghosh, Debashis

AU - Ludena-Rodriguez, Yunin

AU - Kim, Kyoungmi

AU - Ritchie, Marylyn Deriggi

AU - Hertz-Picciotto, Irva

AU - Selleck, Scott Brian

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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, 10: 1470–1480.

AB - 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, 10: 1470–1480.

UR - http://www.scopus.com/inward/record.url?scp=85029665081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029665081&partnerID=8YFLogxK

U2 - 10.1002/aur.1799

DO - 10.1002/aur.1799

M3 - Article

VL - 10

SP - 1470

EP - 1480

JO - Autism Research

JF - Autism Research

SN - 1939-3806

IS - 9

ER -