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Record W3133896960 · doi:10.1101/2021.03.10.21253201

Methylome-wide association study of early life stressors and adult mental health reveals a relationship between birth date and cell type composition in blood

2021· preprint· en· W3133896960 on OpenAlexaff
David M. Howard, Oliver Pain, Ryan Arathimos, Miruna C. Barbu, Carmen Amador, Rosie M. Walker, Bradley Jermy, Mark J. Adams, Ian J. Deary, David J. Porteous, A.M. Campbell, Patrick F. Sullivan, Kathryn L. Evans, Louise Arseneault, Naomi R. Wray, Michael J. Meaney, Andrew M. McIntosh, Cathryn M. Lewis

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsMcGill UniversityDouglas Mental Health University Institute
FundersEconomic and Social Research CouncilBiotechnology and Biological Sciences Research CouncilMedical Research CouncilChief Scientist Office, Scottish Government Health and Social Care DirectorateDirectorate for Biological SciencesSouth London and Maudsley NHS Foundation TrustCentre for Cognitive Ageing and Cognitive EpidemiologyDepartment of Health and Social CareNational Institute for Health and Care ResearchKing's College LondonNational Alliance for Research on Schizophrenia and DepressionUK Research and InnovationScottish Funding CouncilScottish GovernmentWellcome Trust
KeywordsDNA methylationEpigeneticsdNaMCpG siteBiologyMental healthBiomarkerLife course approachMethylationPhysiologyGeneGeneticsMedicinePsychologyDevelopmental psychologyGene expressionPsychiatry

Abstract

fetched live from OpenAlex

Abstract The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes in adulthood are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was assayed at 713,522 CpG sites from 9,537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive data on genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2 and ABI1) were annotated to CpG sites associated with preterm birth (P < 1.27 × 10 −9 ). A further two genes important to the development of sensory pathways (SOBP and RPGRIP1) were annotated to sites associated with low birth weight (P < 4.35 × 10 −8 ). Genes and gene-sets annotated from associated CpGs sites and methylation profile scores were then used to quantify any overlap between the early life environment and mental health traits. However, there was no evidence of any overlap after applying a correction for multiple testing. Time of year of birth was found to be associated with a significant difference in estimated lymphocyte and neutrophil counts. Early life environments influence the risk of developing mental health disorders later in life; however, this study provides no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.025
GPT teacher head0.292
Teacher spread0.267 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2021
Admission routes1
Has abstractyes

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