TY - JOUR
T1 - Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder
AU - Andrews, Shan V.
AU - Ellis, Shannon E.
AU - Bakulski, Kelly M.
AU - Sheppard, Brooke
AU - Croen, Lisa A.
AU - Hertz-Picciotto, Irva
AU - Newschaffer, Craig J.
AU - Feinberg, Andrew P.
AU - Arking, Dan E.
AU - Ladd-Acosta, Christine
AU - Fallin, M. Daniele
N1 - Funding Information:
We thank Eilis Hannon and Jonathan Mill for sharing the complete list of SNPs and 450k probes tested in their fetal brain meQTL analysis. We thank Jianxin Shi for sharing the same list from his lung meQTL study. S.V.A. was supported by the Burroughs-Wellcome Trust training grant: Maryland, Genetics, Epidemiology and Medicine (MD-GEM). The EARLI study was supported by NIEHS R01ES016443 and Autism Speaks grant #260377. The SEED study was supported in part by Autism Speaks #7659, NIEHS (R01ES019001; R01ES017646), and the Centers for Disease Control and Prevention (U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.
AB - Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.
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U2 - 10.1038/s41467-017-00868-y
DO - 10.1038/s41467-017-00868-y
M3 - Article
C2 - 29066808
AN - SCOPUS:85032195304
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1011
ER -