Genetic liability to suicide attempt, suicide death, and psychiatric and substance use disorders on the risk for suicide attempt and suicide death: a Swedish national study

2021 ◽  
pp. 1-10
Author(s):  
Kenneth S. Kendler ◽  
Henrik Ohlsson ◽  
Eve K. Mościcki ◽  
Jan Sundquist ◽  
Alexis C. Edwards ◽  
...  
Keyword(s):  
Suicide Attempt ◽  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Risk Scores ◽  
National Study ◽  
Multivariate Models ◽  
Genetic Liability ◽  
Suicide Death ◽  
Younger Age ◽  
The Impact

Abstract Background How does genetic liability to suicide attempt (SA), suicide death (SD), major depression (MD), bipolar disorder (BD), schizophrenia (SZ), alcohol use disorder (AUD), and drug use disorder (DUD) impact on risk for SA and SD? Methods In the Swedish general population born 1932–1995 and followed through 2017 (n = 7 661 519), we calculate family genetic risk scores (FGRS) for SA, SD, MD, BD, SZ, AUD, and DUD. Registration for SA and SD was assessed from Swedish national registers. Results In univariate and multivariate models predicting SA, FGRS were highest for SA, AUD, DUD, and MD. In univariate models predicting SD, the strongest FGRS were AUD, DUD, SA, and SD. In multivariate models, the FGRS for SA and AUD were higher in predicting SA while the FGRS for SD, BD, and SZ were higher in predicting SD. Higher FGRS for all disorders significantly predicted both younger age at first SA and frequency of attempts. For SD, higher FGRS for MD, AUD, and SD predicted later age at SD. Mediation of FGRS effects on SA and SD was more pronounced for SD than SA, strongest for AUD, DUD, and SZ FGRS and weakest for MD. Conclusions FGRS for both SA and SD and for our five psychiatric disorders impact on risk for SA and SD in a complex manner. While some of the impact of genetic risk factors for psychiatric disorders on risk for SA and SD is mediated through developing the disorders, these risks also predispose directly to suicidal behaviors.

Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits

2021 ◽  
pp. 1-9
Author(s):  
Ikuo Otsuka ◽  
Hanga Galfalvy ◽  
Jia Guo ◽  
Masato Akiyama ◽  
Dan Rujescu ◽  
...  
Keyword(s):  
Suicide Attempt ◽  
Psychiatric Disorders ◽  
Suicidal Behavior ◽  
Statistical Power ◽  
Small Sample ◽  
European Ancestry ◽  
Risk Scores ◽  
Suicide Attempters ◽  
Polygenic Risk ◽  
Suicide Death

Abstract Background Suicidal behavior is moderately heritable and a consequence of a combination of the diathesis traits for suicidal behavior and suicide-related major psychiatric disorders. Here, we sought to examine shared polygenic effects between various psychiatric disorders/traits and suicidal behavior and to compare the shared polygenic effects of various psychiatric disorders/traits on non-fatal suicide attempt and suicide death. Methods We used our genotyped European ancestry sample of 260 non-fatal suicide attempters, 317 suicide decedents and 874 non-psychiatric controls to test whether polygenic risk scores (PRSs) obtained from large GWASs for 22 suicide-related psychiatric disorders/traits were associated with suicidal behavior. Results were compared between non-fatal suicide attempt and suicide death in a sensitivity analysis. Results PRSs for major depressive disorder, bipolar disorder, schizophrenia, ADHD, alcohol dependence, sensitivity to environmental stress and adversity, educational attainment, cognitive performance, and IQ were associated with suicidal behavior (Bonferroni-corrected p < 2.5 × 10−4). The polygenic effects of all 22 psychiatric disorders/traits had the same direction (p for binomial tests = 4.8 × 10−7) and were correlated (Spearman's ρ = 0.85) between non-fatal suicide attempters and suicide decedents. Conclusions We found that polygenic effects for major psychiatric disorders and diathesis-related traits including stress responsiveness and intellect/cognitive function contributed to suicidal behavior. While we found comparable polygenic architecture between non-fatal suicide attempters and suicide decedents based on correlations with PRSs of suicide-related psychiatric disorders/traits, our analyses are limited by small sample size resulting in low statistical power to detect difference between non-fatal suicide attempt and suicide death.

The Prediction of the Course of Minor Psychiatric Disorders

1979 ◽  
Vol 135 (6) ◽  
pp. 535-543 ◽  
Author(s):  
P. J. Huxley ◽  
D. P. Goldberg ◽  
G. P. Maguire ◽  
V. A. Kincey
Keyword(s):  
Psychiatric Disorder ◽  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Clinical Symptoms ◽  
Correlation Factor ◽  
Risk Scores ◽  
Regression Analyses ◽  
Clinical Factors ◽  
One Year ◽  
Minor Psychiatric Disorders

SummaryRecent studies have suggested that psychosocial factors play an important part in the prediction of the course of minor psychiatric disorders. Fifty-nine new psychiatric out-patients suffering from minor disorders were assessed, using standardized clinical and social interviews, and 52 were followed up after one year and the clinical assessment repeated. Social and clinical factors were equally important predictors of the number of months ill in the survey year, but social and constitutional variables were superior in the prediction of percentage change in symptoms over the year.The results of correlation, factor and multiple regression analyses suggest that the course of minor psychiatric disorder is best predicted by three sets of variables which are, in order of importance, the patient's material social circumstances, his clinical symptoms and his ‘genetic risk’ scores.

scholarly journals Applicability of Obesity-Related SNPs and Their Effect Size Measures Defined on Populations with European Ancestry for Genetic Risk Estimation among Roma

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 516 ◽  
Author(s):  
Erand Llanaj ◽  
Péter Pikó ◽  
Károly Nagy ◽  
Gábor Rácz ◽  
Sándor János ◽  
...  
Keyword(s):  
Effect Size ◽  
Genetic Risk ◽  
Association Studies ◽  
Strong Association ◽  
European Ancestry ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Continuous Variables ◽  
Roma Population ◽  
The Impact

Investigations on the impact of genetic factors on the development of obesity have been limited regarding the Roma population—the largest and most vulnerable ethnic minority in Europe of Asian origin. Genetic variants identified from genetic association studies are primarily from European populations. With that in mind, we investigated the applicability of data on selected obesity-related single nucleotide polymorphisms (SNPs), obtained from the Hungarian general (HG) population of European origin, on the Hungarian Roma (HR) population. Twenty preselected SNPs in susceptible alleles, known to be significantly associated with obesity-related phenotypes, were used to estimate the effect of these SNPs on body mass index (BMI) and waist circumference (WC) in HG (N = 1783) and HR (N = 1225) populations. Single SNP associations were tested using linear and logistic regression models, adjusted for known covariates. Out of 20 SNPs, four located in FTO (rs1121980, rs1558902, rs9939609, and rs9941349) showed strong association with BMI and WC as continuous variables in both samples. Computations based on Adult Treatment Panel III (ATPIII) and the International Diabetes Federation’s (IDF) European and Asian criteria showed rs9941349 in FTO to be associated only with WC among both populations, and two SNPs (rs2867125, rs6548238) in TMEM18 associated with WC only in HG population. A substantial difference (both in direction and effect size) was observed only in the case of rs1801282 in PPARγ on WC as a continuous outcome. Findings suggest that genetic risk scores based on counting SNPs with relatively high effect sizes, defined based on populations with European ancestry, can sufficiently allow estimation of genetic susceptibility for Roma. Further studies are needed to clarify the role of SNP(s) with protective effect(s).

scholarly journals Delineating genetic and familial risk for psychopathology in the ABCD study

2020 ◽  
Author(s):  
Clare E Palmer ◽  
Robert John Loughnan ◽  
Carolina Makowski ◽  
Wesley Thompson ◽  
Deanna Barch ◽  
...  
Keyword(s):  
Family History ◽  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Familial Risk ◽  
Risk Scores ◽  
Typically Developing ◽  
Polygenic Risk ◽  
Hyperactivity Disorder ◽  
History Of ◽  
Risk Predictors

Psychiatric disorders place a huge burden on those affected and their families, as well as society. Nearly all psychiatric disorders have a heritable component and lifetime prevalence rates of several disorders are higher among first degree biological relatives of individuals with a diagnosis. Given that many psychiatric disorders have their onset in adolescence, estimating genetic risk during childhood may identify at-risk individuals for early intervention that can reduce this burden. Here we measured genetic risk for psychopathology using both polygenic risk scores (PRS) and family history in a large typically developing sample of 9-10 year old children from the Adolescent Brain and Cognitive Development (ABCD) StudySM and determined associations with a large battery of behavioural phenotypes. By including all genetic risk predictors in the same model, we were able to delineate unique behavioral associations across these measures. Polygenic risk for Attention Deficit Hyperactivity Disorder (ADHD) and depression (DEP) was associated with unique patterns of both externalizing and internalizing behaviors. Family history of conduct problems, depression and anxiety/stress additionally predicted unique behavioral variance across similar measures. These findings provide important insight into the potential predictive utility of PRS and family history in early adolescence and suggest that they may be signaling differential, additive information that could be useful for quantifying risk during development.

scholarly journals GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores

2019 ◽  
Vol 176 (8) ◽  
pp. 651-660 ◽  
Author(s):  
Niamh Mullins ◽  
Tim B. Bigdeli ◽  
Anders D. Børglum ◽  
Jonathan R.I. Coleman ◽  
Ditte Demontis ◽  
...  
Keyword(s):  
Major Depression ◽  
Suicide Attempt ◽  
Psychiatric Disorders ◽  
Risk Scores ◽  
Polygenic Risk

The impact of sex, age at onset, recurrence, mode of ascertainment and medical complications on the family genetic risk score profiles for alcohol use disorder

2021 ◽  
pp. 1-9
Author(s):  
Kenneth S. Kendler ◽  
Henrik Ohlsson ◽  
Jan Sundquist ◽  
Kristina Sundquist
Keyword(s):  
Alcohol Use ◽  
Genetic Risk ◽  
Criminal Behavior ◽  
Alcohol Use Disorder ◽  
Genetic Risk Score ◽  
Age At Onset ◽  
Risk Scores ◽  
Medical Complications ◽  
The Family ◽  
The Impact

Abstract Background Alcohol use disorder (AUD) is clinically heterogeneous. We examine its potential genetic heterogeneity as a function of sex, age, clinical features and mode of ascertainment. Methods In the Swedish population born 1932–1995 (n = 5 829 952), we examined the genetic risk profiles for AUD, major depression (MD), anxiety disorders, bipolar disorder, drug use disorder (DUD), attention deficit-hyperactivity disorder (ADHD) and criminal behavior (CB) in 361 124 cases of AUD subdivided by sex, age at onset (AAO), recurrence, mode of ascertainment and medical complications. Family genetic risk scores (FGRS), calculated from 1st to 5th-degree relatives controlling of cohabitation, assesses genetic risk from phenotypes in the family, not from DNA variants. Results FGRS profiles differed modestly across sex with all scores higher in females. Differences were more pronounced for AAO and recurrence with the FGRS for AUD, DUD, ADHD and CB substantially higher in cases with early AAO or high recurrence rates. Genetic profiles differed considerably by mode of ascertainment, with higher FGRS for AUD and most other disorders in patients seen in hospital v. primary care settings. Cases of AUD with medical complications had higher FGRS for AUD. AUD cases comorbid with MD and DUD had higher FGRS risk for AUD, but this genetic may be less specific given increases in FGRS for multiple other disorders. Conclusions From a genetic perspective, AUD differs substantially as a function of AAO, recurrence, mode of ascertainment and patterns of comorbidity, suggesting caution in cross-sample comparisons of AUD cohorts that differ in these features.

scholarly journals Lower Dietary Intake of Plant Protein Is Associated with Genetic Risk of Diabetes-Related Traits in Urban Asian Indian Adults

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3064
Author(s):  
Sooad Alsulami ◽  
Dhanasekaran Bodhini ◽  
Vasudevan Sudha ◽  
Coimbatore Subramanian Shanthi Rani ◽  
Rajendra Pradeepa ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Protein Intake ◽  
Asian Indians ◽  
Genetic Factors ◽  
Risk Allele ◽  
Plant Protein ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
The Impact ◽  
Lower Plant

The increasing prevalence of type 2 diabetes among South Asians is caused by a complex interplay between environmental and genetic factors. We aimed to examine the impact of dietary and genetic factors on metabolic traits in 1062 Asian Indians. Dietary assessment was performed using a validated semi-quantitative food frequency questionnaire. Seven single nucleotide polymorphisms (SNPs) from the Transcription factor 7-like 2 and fat mass and obesity-associated genes were used to construct two metabolic genetic risk scores (GRS): 7-SNP and 3-SNP GRSs. Both 7-SNP GRS and 3-SNP GRS were associated with a higher risk of T2D (p = 0.0000134 and 0.008, respectively). The 3-SNP GRS was associated with higher waist circumference (p = 0.010), fasting plasma glucose (FPG) (p = 0.002) and glycated haemoglobin (HbA1c) (p = 0.000066). There were significant interactions between 3-SNP GRS and protein intake (% of total energy intake) on FPG (Pinteraction = 0.011) and HbA1c (Pinteraction = 0.007), where among individuals with lower plant protein intake (<39 g/day) and those with >1 risk allele had higher FPG (p = 0.001) and HbA1c (p = 0.00006) than individuals with ≤1 risk allele. Our findings suggest that lower plant protein intake may be a contributor to the increased ethnic susceptibility to diabetes described in Asian Indians. Randomised clinical trials with increased plant protein in the diets of this population are needed to see whether the reduction of diabetes risk occurs in individuals with prediabetes.

scholarly journals Genetic risk scores for major psychiatric disorders and the risk of postpartum psychiatric disorders

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna E. Bauer ◽  
Xiaoqin Liu ◽  
Enda M. Byrne ◽  
Patrick F. Sullivan ◽  
Naomi R. Wray ◽  
...  
Keyword(s):  
Psychiatric Disorder ◽  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Case Control ◽  
Risk Scores ◽  
Psychiatric History ◽  
Genetic Risk Scores ◽  
Increased Risk ◽  
Postpartum Disorders ◽  
Postpartum Psychiatric Disorders

Abstract Postpartum psychiatric disorders are heritable, but how genetic liability varies by other significant risk factors is unknown. We aimed to (1) estimate associations of genetic risk scores (GRS) for major depression (MD), bipolar disorder (BD), and schizophrenia (SCZ) with postpartum psychiatric disorders, (2) examine differences by prior psychiatric history, and (3) compare genetic and familial risk of postpartum psychiatric disorders. We conducted a nested case-control study based on Danish population-based registers of all women in the iPSYCH2012 cohort who had given birth before December 31, 2015 (n = 8850). Cases were women with a diagnosed psychiatric disorder or a filled psychotropic prescription within one year after delivery (n = 5829 cases, 3021 controls). Association analyses were conducted between GRS calculated from Psychiatric Genomics Consortium discovery meta-analyses for MD, BD, and SCZ and case-control status of a postpartum psychiatric disorder. Parental psychiatric history was associated with postpartum psychiatric disorders among women with previous psychiatric history (OR, 1.14; 95% CI 1.02–1.28) but not without psychiatric history (OR, 1.08; 95% CI: 0.81–1.43). GRS for MD was associated with an increased risk of postpartum psychiatric disorders in both women with (OR, 1.44; 95% CI: 1.19–1.74) and without (OR, 1.88; 95% CI: 1.26–2.81) personal psychiatric history. SCZ GRS was only minimally associated with postpartum disorders and BD GRS was not. Results suggest GRS of lifetime psychiatric illness can be applied to the postpartum period, which may provide clues about distinct environmental or genetic elements of postpartum psychiatric disorders and ultimately help identify vulnerable groups.

scholarly journals Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression

2021 ◽  
Author(s):  
Joanna Martin ◽  
Kimiya Asjadi ◽  
Leon Hubbard ◽  
Kimberley Kendall ◽  
Antonio F. Pardiñas ◽  
...  
Keyword(s):  
Mental Health ◽  
Sex Differences ◽  
Family History ◽  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Age At Onset ◽  
Anxiety And Depression ◽  
Rare Cnvs ◽  
Genetic Liability ◽  
History Of

AbstractAnxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset.We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N=4,178, 65.5% female; mean age=41.5 years; N=1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age=45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets.In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD.These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.

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