Abstract
Background: Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features. Objectives: Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children. Methods: We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (~485 000 CpG sites). We also examined associated regions in an independent sample of postmortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available. Results: Using region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)]
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1199-1210 |
| Number of pages | 12 |
| Journal | International Journal of Epidemiology |
| Volume | 44 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 1 2015 |
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Keywords
- Autism risk
- DNA methylation
- Epigenetics
- Sperm
ASJC Scopus subject areas
- Epidemiology
Cite this
Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort. / Feinberg, Jason I.; Bakulski, Kelly M.; Jaffe, Andrew E.; Tryggvadottir, Rakel; Brown, Shannon C.; Goldman, Lynn R.; Croen, Lisa A.; Hertz-Picciotto, Irva; Newschaffer, Craig J.; Daniele Fallin, M.; Feinberg, Andrew P.
In: International Journal of Epidemiology, Vol. 44, No. 4, 01.08.2015, p. 1199-1210.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort
AU - Feinberg, Jason I.
AU - Bakulski, Kelly M.
AU - Jaffe, Andrew E.
AU - Tryggvadottir, Rakel
AU - Brown, Shannon C.
AU - Goldman, Lynn R.
AU - Croen, Lisa A.
AU - Hertz-Picciotto, Irva
AU - Newschaffer, Craig J.
AU - Daniele Fallin, M.
AU - Feinberg, Andrew P.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Background: Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features. Objectives: Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children. Methods: We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (~485 000 CpG sites). We also examined associated regions in an independent sample of postmortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available. Results: Using region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)]
AB - Background: Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features. Objectives: Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children. Methods: We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (~485 000 CpG sites). We also examined associated regions in an independent sample of postmortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available. Results: Using region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)]
KW - Autism risk
KW - DNA methylation
KW - Epigenetics
KW - Sperm
UR - http://www.scopus.com/inward/record.url?scp=84943772575&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943772575&partnerID=8YFLogxK
U2 - 10.1093/ije/dyv028
DO - 10.1093/ije/dyv028
M3 - Article
C2 - 25878217
AN - SCOPUS:84943772575
VL - 44
SP - 1199
EP - 1210
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
SN - 0300-5771
IS - 4
ER -