Polygenic risk scores indicates genetic overlap between peripheral pain syndromes and chronic postsurgical pain

Objective: Shared genetic mechanisms have been hypothesized to explain the comorbidity between ADHD and asthma. To evaluate their genetic overlap, we relied on data from the 1982 Pelotas birth cohort to test the association between polygenic risk scores (PRSs) for ADHD (ADHD-PRSs) and asthma, and PRSs for asthma (asthma-PRSs) and ADHD. Method: We analyzed data collected at birth, 2, 22, and 30 years from 3,574 individuals. Results: Subjects with ADHD had increased risk of having asthma (OR 1.92, 95% CI 1.01–3.66). The association was stronger for females. Our results showed no evidence of association between ADHD-PRSs and asthma or asthma-PRSs and ADHD. However, an exploratory analysis suggested that adult ADHD might be genetically associated with asthma. Conclusion: Our results do not support a shared genetic background between both conditions. Findings should be viewed in light of important limitations, particularly the sample size and the self-reported asthma diagnosis. Studies in larger datasets are required to better explore the genetic overlap between adult ADHD and asthma.

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Genetic and environmental determinants of stressful life events and their overlap with depression and neuroticism

Wellcome Open Research ◽

10.12688/wellcomeopenres.13893.2 ◽

2019 ◽

Vol 3 ◽

pp. 11 ◽

Cited By ~ 6

Author(s):

Toni-Kim Clarke ◽

Yanni Zeng ◽

Lauren Navrady ◽

Charley Xia ◽

Chris Haley ◽

...

Keyword(s):

Risk Factors ◽

Life Events ◽

Stressful Life Events ◽

Family Health ◽

Stressful Life ◽

Risk Scores ◽

Health Study ◽

Phenotypic Variance ◽

Polygenic Risk ◽

Genetic Overlap

Background: Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable and genetic risk for SLEs is associated with risk for MDD. We sought to investigate the genetic and environmental contributions to SLEs in a family-based sample, and quantify genetic overlap with MDD and neuroticism. Methods: A subset of Generation Scotland: the Scottish Family Health Study (GS), consisting of 9618 individuals with information on MDD, past 6 month SLEs, neuroticism and genome-wide genotype data was used in the present study. We estimated the heritability of SLEs using GCTA software. The environmental contribution to SLEs was assessed by modelling familial, couple and sibling components. Using polygenic risk scores (PRS) and LD score regression (LDSC) we analysed the genetic overlap between MDD, neuroticism and SLEs. Results: Past 6-month life events were positively associated with lifetime MDD status (β=0.21, r2=1.1%, p=2.5 x 10-25) and neuroticism (β =0.13, r2=1.9%, p=1.04 x 10-37) at the phenotypic level. Common SNPs explained 8% of the phenotypic variance in personal life events (those directly affecting the individual) (S.E.=0.03, p= 9 x 10-4). A significant effect of couple environment was detected accounting for 13% (S.E.=0.03, p=0.016) of the phenotypic variation in SLEs. PRS analyses found that reporting more SLEs was associated with a higher polygenic risk for MDD (β =0.05, r2=0.3%, p=3 x 10-5), but not a higher polygenic risk for neuroticism. LDSC showed a significant genetic correlation between SLEs and both MDD (rG=0.33, S.E.=0.08 ) and neuroticism (rG=0.15, S.E.=0.07). Conclusions: These findings suggest that SLEs should not be regarded solely as environmental risk factors for MDD as they are partially heritable and this heritability is shared with risk for MDD and neuroticism. Further work is needed to determine the causal direction and source of these associations.

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Improved prediction of schizophrenia by leveraging genetic overlap with brain morphology

10.1101/2020.08.03.20167510 ◽

2020 ◽

Author(s):

Dennis van der Meer ◽

Alexey A Shadrin ◽

Kevin O'Connell ◽

Francesco Bettella ◽

Srdjan Djurovic ◽

...

Keyword(s):

State Of The Art ◽

Imaging Genetics ◽

Brain Morphology ◽

Risk Scores ◽

Brain Disorders ◽

Polygenic Risk ◽

Current State ◽

Genetic Overlap

Schizophrenia is a complex, polygenic disorder associated with subtle, distributed abnormalities in brain morphology. Here, we report large genetic overlap between schizophrenia and brain morphology, which enabled derivation of polygenic risk scores more predictive of schizophrenia diagnosis than the current state-of-the-art. Our results illustrate the potential of exploiting genetic overlap in imaging genetics studies, and how pleiotropy-enriched risk scores may improve prediction of polygenic brain disorders.

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Genetic and environmental determinants of stressful life events and their overlap with depression and neuroticism

Wellcome Open Research ◽

10.12688/wellcomeopenres.13893.1 ◽

2018 ◽

Vol 3 ◽

pp. 11 ◽

Cited By ~ 6

Author(s):

Toni-Kim Clarke ◽

Yanni Zeng ◽

Lauren Navrady ◽

Charley Xia ◽

Chris Haley ◽

...

Keyword(s):

Risk Factors ◽

Life Events ◽

Stressful Life Events ◽

Family Health ◽

Stressful Life ◽

Risk Scores ◽

Health Study ◽

Phenotypic Variance ◽

Polygenic Risk ◽

Genetic Overlap

Background: Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable and genetic risk for SLEs is correlated with risk for MDD. We sought to investigate the genetic and environmental contributions to SLEs in a family-based sample, and quantify genetic overlap with MDD and neuroticism. Methods: A subset of Generation Scotland: the Scottish Family Health Study (GS), consisting of 9618 individuals with information on MDD, past 6 month SLEs, neuroticism and genome-wide genotype data was used in the present study. We estimated the heritability of SLEs using GCTA software. The environmental contribution to SLEs was assessed by modelling familial, couple and sibling components. Using polygenic risk scores (PRS) and LD score regression (LDSC) we analysed the genetic overlap between MDD, neuroticism and SLEs. Results: Past 6-month life events were positively correlated with lifetime MDD status (β=0.21, r2=1.1%, p=2.5 x 10-25) and neuroticism (β =0.13, r2=1.9%, p=1.04 x 10-37) at the phenotypic level. Common SNPs explained 8% of the phenotypic variance in personal life events (those directly affecting the individual) (S.E.=0.03, p= 9 x 10-4). A significant effect of couple environment was detected accounting for 13% (S.E.=0.03, p=0.016) of the phenotypic variation in SLEs. PRS analyses found that reporting more SLEs was associated with a higher polygenic risk for MDD (β =0.05, r2=0.3%, p=3 x 10-5), but not a higher polygenic risk for neuroticism. LDSC showed a significant genetic correlation between SLEs and both MDD (rG=0.33, S.E.=0.08 ) and neuroticism (rG=0.15, S.E.=0.07). Conclusions: These findings suggest that SLEs should not be regarded solely as environmental risk factors for MDD as they are partially heritable and this heritability is shared with risk for MDD and neuroticism. Further work is needed to determine the causal direction and source of these associations.

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P.179 Polygenic risk scores for multiple psychiatric, inflammatory and cardio-metabolic traits highlight possible genetic overlap with suicide attempt

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2020.09.140 ◽

2020 ◽

Vol 40 ◽

pp. S105-S106

Author(s):

G. Fanelli ◽

M. Sokolowski ◽

D. Wasserman ◽

S. Kasper ◽

J. Zohar ◽

...

Keyword(s):

Suicide Attempt ◽

Risk Scores ◽

Polygenic Risk ◽

Metabolic Traits ◽

Genetic Overlap

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The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbz061 ◽

2019 ◽

Cited By ~ 7

Author(s):

Alexander L Richards ◽

Antonio F Pardiñas ◽

Aura Frizzati ◽

Katherine E Tansey ◽

Amy J Lynham ◽

...

Keyword(s):

Association Studies ◽

Risk Scores ◽

Polygenic Risk Score ◽

Genome Wide Association Studies ◽

Related Factors ◽

Polygenic Risk ◽

Genome Wide ◽

A Genome ◽

Genetic Overlap ◽

Individual Variant

Abstract Background Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. Methods We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases. Results PRS for both population IQ (P = 4.39 × 10–28) and EA (P = 1.27 × 10–26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS. Conclusions Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

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The use of Polygenic Risk Scores to Inform Aetiology of Mood and Psychotic Disorders

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2051 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S166-S166

Author(s):

J. Harrison ◽

S. Mistry

Keyword(s):

Bipolar Disorder ◽

Genetic Basis ◽

Psychotic Disorders ◽

Mental Illnesses ◽

Risk Scores ◽

Psychotic Symptoms ◽

Polygenic Risk ◽

Genetic Overlap ◽

Competing Interest

IntroductionPolygenic risk scores (PRS) incorporate many small genetic markers that are associated with conditions. This technique was first used to investigate mental illnesses in 2009. Since then, it has been widely used.ObjectivesWe wanted to explore how PRS have been used to the study the aetiology of psychosis, schizophrenia, bipolar disorder and depression.AimsWe aimed to conduct a systematic review, identifying studies that have examined associations between PRS for bipolar disorder, schizophrenia/psychosis and depression and psychopathology-related outcome measures.MethodsWe searched EMBASE, Medline and PsychInfo from 06/08/2009 to 14/03/2016. We hand-searched the reference lists of related papers.ResultsAfter removing duplicates, the search yielded 1043 publications. When irrelevant articles were excluded, 33 articles remained. We found 24 studies using schizophrenia PRS, three using bipolar PRS and nine using depression PRS. Many studies successfully used PRS to predict case/control status. Some studies showed associations between PRS and diagnostic sub-categories. A range of clinical phenotypes and symptoms has been explored. For example, specific PRS are associated with cognitive performance in schizophrenia, psychotic symptoms in bipolar disorder, and frequency of episodes of depression. PRS have also demonstrated genetic overlap between mental illnesses. It was difficult to assess the quality of some studies as not all reported sufficient methodological detail.ConclusionsPRS have enabled us to explore the polygenic architecture of mental illness and demonstrate a genetic basis for some observed features. However, they have yet to give insights into the biology, which underpin mental illnesses.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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