scholarly journals Childhood trajectories of internalising and externalising problems associated with a polygenic risk score for neuroticism in a UK birth cohort study

2021 ◽  
Author(s):  
Ilaria Costantini ◽  
Hannah Sallis ◽  
Daniel Major-Smith ◽  
Kate Tilling ◽  
Rebecca M Pearson ◽  
...  
Keyword(s):  
Cohort Study ◽  
Birth Cohort ◽  
Risk Score ◽  
Psychological Outcomes ◽  
Birth Cohort Study ◽  
Polygenic Risk Score ◽  
Mixed Effect ◽  
Polygenic Risk ◽  
Externalising Problems ◽  
Internalising Problems

Neuroticism represents a personality disposition towards experiencing negative emotions more frequently and intensely. Longitudinal studies suggest that neuroticism increases risk of several psychological and physical problems. Improved understanding of how this trait manifests in early life could help inform preventative strategies in those liable to neuroticism. This study explored how a polygenic risk score (PRS) for neuroticism is expressed from infancy to late childhood across various psychological outcomes and how it associates with trajectories of internalising and externalising problems from ages 4-11 in the Avon Longitudinal Study of Parents and Children (N=5,279). We employed multivariable linear and ordinal regression models to estimate associations between a child neuroticism PRS and psychological outcomes. A three-level mixed-effect model was employed to characterise child internalising and externalising trajectories and estimate how a child PRS associated with both their overall levels and rates of change. We found evidence that the PRS for neuroticism was associated with a more sensitive temperament in early infancy in addition to higher emotional and behavioural problems and a higher risk of being diagnosed with a variety of clinical disorders, particularly anxiety disorders, in childhood. We also found strong evidence that the PRS for neuroticism was associated with overall levels of internalising and externalising trajectories, with a larger magnitude of effect on the internalising trajectory. The PRS was also associated with slower rates of reduction of internalising problems. Our findings using a large, well-characterised birth cohort study suggest that phenotypic manifestations of a PRS for adult neuroticism can be detected as early as in infancy and that this PRS associates with several mental health problems and differences in emotional trajectories across childhood.

scholarly journals Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants

BMJ ◽  
2018 ◽  
pp. k4168 ◽  
Author(s):  
Loes CA Rutten-Jacobs ◽  
Susanna C Larsson ◽  
Rainer Malik ◽  
Kristiina Rannikmäe ◽  
Cathie L Sudlow ◽  
...  
Keyword(s):  
Cohort Study ◽  
Risk Score ◽  
Genetic Risk ◽  
Cox Regression ◽  
Healthy Lifestyle ◽  
Lifestyle Factors ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Increased Risk

AbstractObjectiveTo evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.DesignProspective population based cohort study.SettingUK Biobank Study, UK.Participants306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.Main outcome measureHazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was constructed at P<1×10−5to test for an association with incident stroke. Adherence to a healthy lifestyle was determined on the basis of four factors: non-smoker, healthy diet, body mass index <30 kg/m2, and regular physical exercise.ResultsDuring a median follow-up of 7.1 years (2 138 443 person years), 2077 incident strokes (1541 ischaemic stroke, 287 intracerebral haemorrhage, and 249 subarachnoid haemorrhage) were ascertained. The risk of incident stroke was 35% higher among those at high genetic risk (top third of polygenic score) compared with those at low genetic risk (bottom third): hazard ratio 1.35 (95% confidence interval 1.21 to 1.50), P=3.9×10−8. Unfavourable lifestyle (0 or 1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3 or 4 healthy lifestyle factors): 1.66 (1.45 to 1.89), P=1.19×10−13. The association with lifestyle was independent of genetic risk stratums.ConclusionIn this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasise the benefit of entire populations adhering to a healthy lifestyle, independent of genetic risk.

F36. Obsessive-Compulsive symptoms, Polygenic Risk Score and Thalamic Development in Children From the Brazilian High-Risk Cohort Study

2019 ◽  
Vol 85 (10) ◽  
pp. S226
Author(s):  
Beatriz Ravagnani ◽  
Marcelo Hoexter ◽  
Marcos Santoro ◽  
James Leckman ◽  
Pedro Pan ◽  
...  
Keyword(s):  
Cohort Study ◽  
High Risk ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Obsessive Compulsive ◽  
Obsessive Compulsive Symptoms ◽  
Polygenic Risk ◽  
High Risk Cohort

scholarly journals Parental inflammatory bowel disease and autism in the offspring: Triangulating the evidence using four complementary study designs.

2021 ◽  
Author(s):  
Aws Sadik ◽  
Christina Dardani ◽  
Panagiota Pagoni ◽  
Alexandra Havdahl ◽  
Evie Stergiakouli ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cohort Study ◽  
Genetic Correlation ◽  
Risk Score ◽  
Bowel Disease ◽  
Causal Effect ◽  
Polygenic Risk Score ◽  
Genetic Liability ◽  
Polygenic Risk ◽  
Inflammatory Bowel

Importance: Evidence linking parental diagnoses of inflammatory bowel disease (IBD) with offspring autism is inconclusive. Objective: To investigate associations between parental diagnoses of IBD and offspring autism and elucidate their underlying aetiology by conducting four complementary studies. Design, Setting and Participants: (1) Nationwide population-based cohort study using Swedish registers to examine associations between parental IBD diagnoses and autism diagnoses in offspring, (2) Linkage disequilibrium (LD)-score regression to estimate the genetic correlation between the phenotypes. (3) Polygenic risk score (PRS) analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate associations between maternal genetic liability to IBD and autism factor mean score in offspring. (4) Two-sample Mendelian randomization (MR) to assess bidirectional causal links between genetic liability to IBD and autism. Results: Observational analyses provided evidence of an association between parental IBD diagnoses and offspring autism diagnosis in mutually adjusted models (maternal: OR= 1.32; 95%CI: 1.25 to 1.40; p<0.001; paternal: OR= 1.09; 95%CI: 1.02 to 1.17; p=0.012; n= 2 324 227, 52.3% male). PRS analyses in ALSPAC indicated associations between maternal PRS for IBD subtypes and a measure of broad autism phenotype, autism factor mean score, in the offspring (UC: b=0.02; 95%CI: 0.003 to 0.05; p= 0.02; R2= 0.06; Crohn's: b= 0.03; 95%CI: 0.01 to 0.05; p= 0.004; R2= 0.06; n= 7357, 50.3% male).MR analyses provided evidence of a potential causal effect of genetic liability for IBD, especially ulcerative colitis, on autism (OR= 1.03; 95%CI: 1.01 to 1.06). There was little evidence to suggest a causal effect of genetic liability to autism on risk of IBD, or a genetic correlation between the two conditions. Conclusions and relevance: Triangulating evidence from a nationwide register-based cohort study, genetic correlation, polygenic risk score analyses and MR, we found evidence of a potentially causal link between parental, particularly maternal, diagnoses and genetic liability to IBD and offspring autism. Perinatal immune system dysregulation, micronutrient malabsorption and anaemia may be implicated.

scholarly journals Polygenic Risk Score Improves Prostate Cancer Risk Prediction: Results from the Stockholm-1 Cohort Study

2011 ◽  
Vol 60 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Markus Aly ◽  
Fredrik Wiklund ◽  
Jianfeng Xu ◽  
William B. Isaacs ◽  
Martin Eklund ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cohort Study ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Risk Score ◽  
Prostate Cancer Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk
Sign in / Sign up

Export Citation Format

Share Document