Journal club 20201123

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# Journal club 
## November 23, 2020

<img src="IEU-logo-colour.png" width="50%">
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MRC Integrative Epidemiology Unit    
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## EWAS in infant samples

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|     pmid|title                                                                                                                                                  |journal             |variable                 |tissue                   |n                   |assocs                           |notes                                                            |
|--------:|:-------------------------------------------------------------------------------------------------------------------------------------------------------|:-------------------|:------------------------|:------------------------|:-------------------|:--------------------------------|:----------------------------------------------------------------|
| 33076993|Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants.                                             |Clin Epigenetics    |neonatal morbidity score |buccal                   |532                 |10                               |                                                                 |
| 33184255|Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis.                                            |Transl Psychiatry   |ADHD                     |cord blood; blood (7-11) |2477;2374           |9;none                           |PACE study                                                       |
]

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## EWAS in child samples

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|     pmid|title                                                                                                                                                  |journal             |variable                 |tissue                   |n                   |assocs                           |notes                                                            |
|--------:|:-------------------------------------------------------------------------------------------------------------------------------------------------------|:-------------------|:------------------------|:------------------------|:-------------------|:--------------------------------|:----------------------------------------------------------------|
| 33137917|Association between Breastfeeding and DNA Methylation over the Life Course... |Nutrients           |breastfeeding            |blood                    |640 (7)             |1                                |ALSPAC data; some agreement at age 15-17                         |
| 33173928|Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.                                                             |medRxiv             |violence/stress          |blood (9-20)             |487                 |gun violence=1;maternal stress=2 |a few top sites associated with asthma    |
| 33150670|Sex-specific associations of asthma acquisition with changes in DNA methylation during adolescence.                                                     |Clin Exp Allergy    |asthma                   |blood                    |275 (10-18)         |535                              |sex interactions at 13 sites, most replicated               |
]

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## EWAS in adult samples

.striped[
|     pmid|title                                                                                                                                                  |journal             |variable                 |tissue                   |n                   |assocs                           |notes                                                            |
|--------:|:-------------------------------------------------------------------------------------------------------------------------------------------------------|:-------------------|:------------------------|:------------------------|:-------------------|:--------------------------------|:----------------------------------------------------------------|
| 33178681|DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA.                                                                           |Front Cell Dev Biol |diabetic kidney disease  |blood                    |250 |22                               |all have type 2 diabetes                                         |
| 33152445|PTSD is associated with increased DNA methylation across regions of HLA-DPB1 and SPATC1L.                                                               |Brain Behav Immun   |PTSD                     |blood                    |367                 |2 DMRs                           |Grady Trauma Project, DMRs by bumphunter!                        |
| 33134824|EWAS Using Prediagnostic Bloods Identifies New Genomic Regions Associated With Pancreatic Cancer Risk.                      |JNCI Cancer Spectr  |pancreatic cancer        |blood at baseline        |824                 |0                                |no predictor due to lack of consistency between training/testing |
| 33100131|EWAS identifies DNA methylation sites associated with target organ damage in older African Americans.                       |Epigenetics         |target organ damage      |blood                    |961                 |7                                |used multi-trait regression model                                |
]

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<img src="cell.png" width="65%">
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.box[
A new lab method, **SHARE-seq**, generates simultaneous single-cell ATAC-seq and RNA-seq.
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**Main finding:** during lineage commitment, chromatin accessibility precedes gene expression.
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* Generate single-cell chromatin accessibility and 3D chromatin interactions across multiple brain regions
* Predict functional SNPs for AD and PD 
* Predict genome targets for AD/PD GWAS hits
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## Background

* Incidence of gestational diabetes is increasing

* Obesity is a risk factor

* Exposure to gestational diabetes is a risk factor for obesity ...

* Questions
    - What can be done?
    - Does DNA methylation play a role?

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## Data

* *UK Pregnancies Better Eating and Activity Trial (UPBEAT)*

RCT of lifestyle intervention (low glycaemic index diet plus physical activity) for obese women

* Cord blood DNA methylation in 557 newborns

## Methods

* Test DNAm differences due to exposure to gestational diabetes milletus

* Ask if these differences are attenuated by the intervention

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## DNAm differences due to GDM

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<img src="pm-table2.png" width="85%">
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<img src="pm-venn.png" width="30%">
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## DNAm differences with/without the intervention

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.larger[
*Is this the best way to show this?*
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## Things to consider

* EWAS agreement between fasting glucose and other measures low

* EWAS agreement between the sexes very low

* The intervention did not reduce GDM and had no associations with DNAm

(but did decrease "skinfold thickness and gestational weight gain and improved metabolome" in the mothers, and reduced "subscapsular skinfold thickness z-score at age 6 months" in infants)

* We still haven't answered if cord DNAm changes matter.