scholarly journals Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors

2021 ◽  
Author(s):  
Niamh Mullins ◽  
Jooeun Kang ◽  
Adrian I. Campos ◽  
Jonathan R.I. Coleman ◽  
Alexis C. Edwards ◽  
...  
Keyword(s):  
Risk Factors ◽  
Suicide Attempt ◽  
Psychiatric Disorders ◽  
Genetic Architecture ◽  
Shared Genetic

scholarly journals Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors

2020 ◽  
Author(s):  
Niamh Mullins ◽  
Jooeun Kang ◽  
Adrian I Campos ◽  
Jonathan R I Coleman ◽  
Alexis C Edwards ◽  
...  
Keyword(s):  
Risk Factors ◽  
Suicide Attempt ◽  
Psychiatric Disorders ◽  
Risk Taking ◽  
Sleep Disturbances ◽  
Genetic Correlations ◽  
Genetic Etiology ◽  
Genome Wide ◽  
A Genome ◽  
Shared Genetic

AbstractSuicide is a leading cause of death worldwide and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both are known to have a substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium and conditioned the results on psychiatric disorders using GWAS summary statistics, to investigate their shared and divergent genetic architectures. Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated after conditioning and has previously been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, lower socioeconomic status, pain, lower educational attainment, reproductive traits, risk-taking, sleep disturbances, and poorer overall general health. After conditioning, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest the existence of a shared genetic etiology between SA and known risk factors that is not mediated by psychiatric disorders.

Shared genetic architecture across psychiatric disorders

2021 ◽  
pp. 1-7
Author(s):  
Andrew D. Grotzinger
Keyword(s):  
Risk Factors ◽  
Psychiatric Disorders ◽  
Genetic Correlations ◽  
Fine Grained ◽  
Level Data ◽  
Symptom Level ◽  
Genetic Level ◽  
Genetic Signal ◽  
Family Based ◽  
Shared Genetic

Abstract Psychiatric disorders overlap substantially at the genetic level, with family-based methods long pointing toward transdiagnostic risk pathways. Psychiatric genomics has progressed rapidly in the last decade, shedding light on the biological makeup of cross-disorder risk at multiple levels of analysis. Over a hundred genetic variants have been identified that affect multiple disorders, with many more to be uncovered as sample sizes continue to grow. Cross-disorder mechanistic studies build on these findings to cluster transdiagnostic variants into meaningful categories, including in what tissues or when in development these variants are expressed. At the upper-most level, methods have been developed to estimate the overall shared genetic signal across pairs of traits (i.e. single-nucleotide polymorphism-based genetic correlations) and subsequently model these relationships to identify overarching, genomic risk factors. These factors can subsequently be associated with external traits (e.g. functional imaging phenotypes) to begin to understand the makeup of these transdiagnostic risk factors. As psychiatric genomic efforts continue to expand, we can begin to gain even greater insight by including more fine-grained phenotypes (i.e. symptom-level data) and explicitly considering the environment. The culmination of these efforts will help to inform bottom-up revisions of our current nosology.

scholarly journals Disease Risk Factors Identified Through Shared Genetic Architecture and Electronic Medical Records

2014 ◽  
Vol 6 (234) ◽  
pp. 234ra57-234ra57 ◽  
Author(s):  
L. Li ◽  
D. J. Ruau ◽  
C. J. Patel ◽  
S. C. Weber ◽  
R. Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Electronic Medical Records ◽  
Medical Records ◽  
Genetic Architecture ◽  
Disease Risk ◽  
Shared Genetic

scholarly journals The genetic relationship between female reproductive traits and six psychiatric disorders

2018 ◽  
Author(s):  
Guiyan Ni ◽  
Azmeraw Amare ◽  
Xuan Zhou ◽  
Natalie Mills ◽  
Jacob Gratten ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Correlation ◽  
Genetic Architecture ◽  
Reproductive Traits ◽  
P Value ◽  
Age At First Birth ◽  
Potential Implication ◽  
Positive Effects ◽  
Female Reproductive Traits ◽  
Shared Genetic

ABSTRACTFemale reproductive behaviors have an important implication in evolutionary fitness and health of offspring. Previous studies have shown that age at first birth of women (AFB) is genetically associated with schizophrenia (SCZ). However, for most other psychiatric disorders and reproductive traits, the latent shared genetic architecture is largely unknown. Here we used the second wave of UK Biobank data (N=220,685) to evaluate the association between five female reproductive traits and polygenetic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N=429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with AFB (genetic correlation of −0.68 ± 0.03 with p-value = 1.86E-89), age at first sexual intercourse (AFS) (−0.56 ± 0.03 with p-value = 3.42E-60), number of live births (NLB) (0.36 ± 0.04 with p-value = 4.01E-17) and age at menopause (−0.27 ± 0.04 with p-value = 5.71E-13). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (genetic correlation of 0.35 ± 0.06), ED and AFS (0.19 0.06), Major depressive disorder (MDD) and AFB (−0.27 ± 0.07), MDD and AFS (− 0.27 ± 0.03) and SCZ and AFS (−0.10 ± 0.03). Our findings reveal the shared genetic architecture between the five reproductive traits in women and six psychiatric disorders, which have a potential implication that helps to improve reproductive health in women, hence better child outcomes. Our findings may also explain, at least in part, an evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.

Prevalence of and Risk Factors for Suicide Attempts Among Patients With Severe Psychiatric Disorders in Eastern Morocco

Crisis ◽  
2021 ◽  
Author(s):  
Mohammed Barrimi ◽  
Khalid Serraj ◽  
Ismail Rammouz ◽  
Rachid Alouane ◽  
Najoua Messaoudi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Suicide Attempt ◽  
Psychiatric Disorders ◽  
Suicide Attempts ◽  
Personal History ◽  
University Hospital ◽  
Number Of Patients ◽  
History Of ◽  
Risk Factors For Suicide

Abstract. Background: Suicide attempts are common in patients with severe psychiatric disorders; however, they are rarely studied in this population. Aims: To investigate the prevalence and risk factors associated with suicide attempts among patients with severe psychiatric disorders. Method: This is a cross-sectional study of patients admitted to the Mohammed VI University Hospital of Psychiatry in Oujda, Morocco. Results: A total of 250 patients with a psychiatric disorder were recruited in this study. Among these, 78 cases (31.2%) had a personal history of suicide attempts. A personal history of suicide attempt was significantly higher among women compared to men (45.5% vs. 27.2%, p = .0099). The most common method of suicide attempts was jumping from heights (31%). Patients with a personal history of suicide attempts had a significantly higher prevalence of alcohol consumption ( p = .0063), family history of psychiatric disorders ( p = .002), family history of suicide attempt ( p = .00004), and family history of suicide ( p = .018) compared to those who had never made suicide attempts. Limitations: As suicidal behavior is highly stigmatized in Morocco, the number of patients who have made a suicide attempt may be underestimated. Conclusion: Our findings justify the need to provide specialized support to psychiatric patients with risk factors for suicide attempts.

A twin study of genetic and environmental influences on suicidality in men

2002 ◽  
Vol 32 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Q. FU ◽  
A. C. HEATH ◽  
K. K. BUCHOLZ ◽  
E. C. NELSON ◽  
A. L. GLOWINSKI ◽  
...  
Keyword(s):  
Risk Factors ◽  
Suicidal Ideation ◽  
Suicide Attempt ◽  
Conduct Disorder ◽  
Regression Model ◽  
Psychiatric Disorders ◽  
Multinomial Logistic Regression ◽  
Combat Exposure ◽  
Genetic Influences ◽  
Childhood Conduct

Background. Previous studies that have examined genetic influences on suicidal behaviour were confounded by genetic vulnerability for psychiatric risk factors. The present study examines genetic influences on suicidality (i.e. suicidal ideation and/or suicide attempt) after controlling for the inheritance of psychiatric disorders.Methods. Sociodemographics, combat exposure, lifetime DSM-III-R major depression, bipolar disorder, childhood conduct disorder, adult antisocial personality disorder, panic disorder, post-traumatic stress disorder, drug dependence, alcohol dependence and lifetime suicidal ideation and attempt were assessed in 3372 twin pairs from the Vietnam Era Twin Registry who were assessed in 1987 and 1992. Genetic risk factors for suicidality were examined in a multinomial logistic regression model. Additive genetic, shared environmental and non-shared environmental effects on suicidality were estimated using structural equation modelling, controlling for other risk factors.Results. The prevalence of suicidal ideation and suicide attempt were 16·1% and 2·4% respectively. In a multinomial regression model, co-twin’s suicidality, being white, unemployment, being other than married, medium combat exposure and psychiatric disorders were significant predictors for suicidal ideation. Co-twin’s suicidality, unemployment, marital disruption, low education attainment and psychiatric disorders (except childhood conduct disorder) were significant predictors for suicide attempt. Model-fitting suggested that suicidal ideation was influenced by additive genetic (36%) and non-shared environmental (64%) effects, while suicide attempt was affected by additive genetic (17%), shared environmental (19%) and non-shared environmental (64%) effects.Conclusions. There may be a genetic susceptibility specific to both suicidal ideation and suicide attempt in men, which is not explained by the inheritance of common psychiatric disorders.

scholarly journals Polygenic overlap and shared genetic loci between loneliness, severe mental disorders, and cardiovascular disease risk factors suggest shared molecular mechanisms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Linn Rødevand ◽  
Shahram Bahrami ◽  
Oleksandr Frei ◽  
Aihua Lin ◽  
Osman Gani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Mental Disorders ◽  
Genetic Architecture ◽  
Molecular Mechanisms ◽  
Cvd Risk Factors ◽  
Genetic Loci ◽  
Severe Mental Disorders ◽  
Cvd Risk ◽  
Shared Genetic

AbstractClinical and epidemiological evidence suggest that loneliness is associated with severe mental disorders (SMDs) and increases the risk of cardiovascular disease (CVD). However, the mechanisms underlying the relationship between loneliness, SMDs, and CVD risk factors remain unknown. Here we explored overlapping genetic architecture and genetic loci shared between SMDs, loneliness, and CVD risk factors. We analyzed large independent genome-wide association study data on schizophrenia (SCZ), bipolar disorder (BD), major depression (MD), loneliness and CVD risk factors using bivariate causal mixture mode (MiXeR), which estimates the total amount of shared variants, and conditional false discovery rate to evaluate overlap in specific loci. We observed substantial genetic overlap between SMDs, loneliness and CVD risk factors, beyond genetic correlation. We identified 149 loci jointly associated with loneliness and SMDs (MD n = 67, SCZ n = 54, and BD n = 28), and 55 distinct loci jointly associated with loneliness and CVD risk factors. A total of 153 novel loneliness loci were found. Most of the shared loci possessed concordant effect directions, suggesting that genetic risk for loneliness may increase the risk of both SMDs and CVD. Functional analyses of the shared loci implicated biological processes related to the brain, metabolic processes, chromatin and immune system. Altogether, the study revealed polygenic overlap between loneliness, SMDs and CVD risk factors, providing new insights into their shared genetic architecture and common genetic mechanisms.

scholarly journals Exploring the shared genetic architecture of modifiable risk factors and related endophenotypes of Alzheimer’s disease: A genomic SEM study

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Isabelle F. Foote ◽  
Benjamin M. Jacobs ◽  
Alastair J. Noyce ◽  
Ania Korszun ◽  
Kamaldeep S. Bhui ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Architecture ◽  
Modifiable Risk Factors ◽  
Sem Study ◽  
Shared Genetic

scholarly journals Causal effect of C-reactive protein and vitamin D on human cerebral anatomy observed among genetically correlated biomarkers in blood

2021 ◽  
Author(s):  
Dylan James Kiltschewskij ◽  
William R Reay ◽  
Murray J Cairns
Keyword(s):  
Vitamin D ◽  
Psychiatric Disorders ◽  
Cortical Thickness ◽  
Genetic Architecture ◽  
Causal Effect ◽  
Causal Relationships ◽  
C Reactive Protein ◽  
Biochemical Traits ◽  
Reactive Protein ◽  
Shared Genetic

Psychiatric disorders such as schizophrenia are commonly associated with structural brain alterations affecting the cortex, which frequently vary with clinically relevant factors including antipsychotic treatment, duration of illness and age of onset. While the underlying variables mediating these structural changes are poorly understood, recent genetic evidence suggests circulating metabolites and other biochemical traits play a causal role in a number of psychiatric disorders which could be mediated by changes in the cerebral cortex. In the current study, we leveraged publicly available genome-wide association study (GWAS) data to explore shared genetic architecture and evidence for causal relationships between a panel of 50 biochemical traits and measures of cortical thickness and surface area at both the global and regional levels. Linkage disequilibrium score regression identified a total of 20 significant and 156 suggestive genetically correlated biochemical-cortical trait pairings, of which six exhibited strong evidence for causality in a latent causal variable model. Interestingly, a negative causal relationship was identified between a unit increase in serum C-reactive protein levels and thickness of the lingual and lateral occipital regions that was also supported by Mendelian randomisation, while circulating vitamin D (25-hydroxyvitamin D) levels exhibited a positive causal effect on temporal pole thickness. Taken together, our findings suggest a subset of biochemical traits exhibit shared genetic architecture and potentially causal relationships with cortical thickness in functionally distinct regions, which may contribute to alteration of cortical structure in psychiatric disorders.

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