TY  - JOUR
A1  - Vangeel, Elise Beau
A1  - Pishva, Ehsan
A1  - Hompes, Titia
A1  - van den Hove, Daniel
A1  - Lambrechts, Diether
A1  - Allegaert, Karel
A1  - Freson, Kathleen
A1  - Izzi, Benedetta
A1  - Claes, Stephan
T1  - Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for \(GABBR1\)
JF  - Clinical Epigenetics
N2  - Background: There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach.
Methods: We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome-wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n = 45) and candidate gene methylation using EpiTYPER (n = 80). Cortisol levels were measured at 2, 4, and 12 months of age to test infant stress system (re)activity.
Results: Data showed ten differentially methylated regions (DMR) when comparing newborns exposed to low versus high pregnancy anxiety scores. We validated a top DMR in the GABA-B receptor subunit 1 gene (GABBR1) revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R = 0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant cortisol levels in response to a routine vaccination at 4 months old.
Conclusions: In conclusion, our results show that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that our candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research.
KW  - DNA methylation
KW  - GABBR1
KW  - gender differences
KW  - HPA axis
KW  - pregnancy anxiety
KW  - prenatal stress
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173825
VL  - 9
ER  - 
TY  - JOUR
A1  - Westbury, Sarah K
A1  - Turro, Ernest
A1  - Greene, Daniel
A1  - Lentaigne, Claire
A1  - Kelly, Anne M
A1  - Bariana, Tadbir K
A1  - Simeoni, Ilenia
A1  - Pillois, Xavier
A1  - Attwood, Antony
A1  - Austin, Steve
A1  - Jansen, Sjoert BG
A1  - Bakchoul, Tamam
A1  - Crisp-Hihn, Abi
A1  - Erber, Wendy N
A1  - Favier, Rémi
A1  - Foad, Nicola
A1  - Gattens, Michael
A1  - Jolley, Jennifer D
A1  - Liesner, Ri
A1  - Meacham, Stuart
A1  - Millar, Carolyn M
A1  - Nurden, Alan T
A1  - Peerlinck, Kathelijne
A1  - Perry, David J
A1  - Poudel, Pawan
A1  - Schulman, Sol
A1  - Schulze, Harald
A1  - Stephens, Jonathan C
A1  - Furie, Bruce
A1  - Robinson, Peter N
A1  - van Geet, Chris
A1  - Rendon, Augusto
A1  - Gomez, Keith
A1  - Laffan, Michael A
A1  - Lambert, Michele P
A1  - Nurden, Paquita
A1  - Ouwehand, Willem H
A1  - Richardson, Sylvia
A1  - Mumford, Andrew D
A1  - Freson, Kathleen
T1  - Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders
JF  - Genome Medicine
N2  - Background: 
Heritable bleeding and platelet disorders (BPD) are heterogeneous and frequently have an unknown genetic basis. The BRIDGE-BPD study aims to discover new causal genes for BPD by high throughput sequencing using cluster analyses based on improved and standardised deep, multi-system phenotyping of cases. 
Methods: 
We report a new approach in which the clinical and laboratory characteristics of BPD cases are annotated with adapted Human Phenotype Ontology (HPO) terms. Cluster analyses are then used to characterise groups of cases with similar HPO terms and variants in the same genes. Results: 
We show that 60% of index cases with heritable BPD enrolled at 10 European or US centres were annotated with HPO terms indicating abnormalities in organ systems other than blood or blood-forming tissues, particularly the nervous system. Cases within pedigrees clustered closely together on the bases of their HPO-coded phenotypes, as did cases sharing several clinically suspected syndromic disorders. Cases subsequently found to harbour variants in ACTN1 also clustered closely, even though diagnosis of this recently described disorder was not possible using only the clinical and laboratory data available to the enrolling clinician. 
Conclusions: 
These findings validate our novel HPO-based phenotype clustering methodology for known BPD, thus providing a new discovery tool for BPD of unknown genetic basis. This approach will also be relevant for other rare diseases with significant genetic heterogeneity.
KW  - disease
KW  - thrombocytopenia
KW  - guidelines
KW  - complex
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143329
VL  - 7
IS  - 36
ER  -