Dataset Information

Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study.

ABSTRACT: Family studies have shown an aggregation of suicidal behavior in families. Yet, molecular studies are needed to identify loci accounting for genetic heritability. We conducted a genome-wide association study and estimated single nucleotide polymorphisms (SNP) heritability for a suicide attempt. In a case-cohort study, national data on all individuals born in Denmark after 1981 and diagnosed with severe mental disorders prior to 2013 (n?=?57,377) and individuals from the general population (n?=?30,000) were obtained. After quality control, the sample consisted of 6024 cases with an incidence of suicide attempt and 44,240 controls with no record of a suicide attempt. Suggestive associations between SNPs, rs6880062 (p-value: 5.4?×?10^-8) and rs6880461 (p-value: 9.5?×?10^-8), and suicide attempt were identified when adjusting for socio-demographics. Adjusting for mental disorders, three significant associations, all on chromosome 20, were identified: rs4809706 (p-value: 2.8?×?10^-8), rs4810824 (p-value: 3.5?×?10^-8), and rs6019297 (p-value: 4.7?×?10⁸). Sub-group analysis of cases with affective disorders revealed SNPs associated with suicide attempts when compared to the general population for gene PDE4B. All SNPs explained 4.6% [CI-95: 2.9-6.3%] of the variation in suicide attempt. Controlling for mental disorders reduced the heritability to 1.9% [CI-95: 0.3-3.5%]. Affective and autism spectrum disorders exhibited a SNP heritability of 5.6% [CI-95: 1.9-9.3%] and 9.6% [CI-95: 1.1-18.1%], respectively. Using the largest sample to date, we identified significant SNP associations with suicide attempts and support for a genetic transmission of suicide attempt, which might not solely be explained by mental disorders.

SUBMITTER: Erlangsen A

PROVIDER: S-EPMC7515833 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study.

Erlangsen Annette A Appadurai Vivek V Wang Yunpeng Y Turecki Gustavo G Mors Ole O Werge Thomas T Mortensen Preben B PB Starnawska Anna A Børglum Anders D AD Schork Andrew A Nudel Ron R Bækvad-Hansen Marie M Bybjerg-Grauholm Jonas J Hougaard David M DM Thompson Wesley K WK Nordentoft Merete M Agerbo Esben E

Molecular psychiatry 20180816 10

Family studies have shown an aggregation of suicidal behavior in families. Yet, molecular studies are needed to identify loci accounting for genetic heritability. We conducted a genome-wide association study and estimated single nucleotide polymorphisms (SNP) heritability for a suicide attempt. In a case-cohort study, national data on all individuals born in Denmark after 1981 and diagnosed with severe mental disorders prior to 2013 (n = 57,377) and individuals from the general population (n = 3 ...[more]

PMID: 30116032

Similar Datasets

Project description:ImportanceClarification of the joint influence of familial patterns of suicide attempts and comorbid mental disorders can enhance the understanding and prevention of suicide attempts.ObjectiveTo investigate the familial patterns of suicide attempts and comorbid mental disorders and their associations in a 2-site family study of mood and anxiety disorders.Design, setting, and participantsData were obtained from 2 parallel community-based family studies conducted in the United States (National Institute of Mental Health [NIMH] study) and in Lausanne, Switzerland (PsyCoLaus study), on the comorbidity of mood and anxiety disorders. The study sample comprised 1119 adult probands and 5355 first-degree relatives. Data were collected and analyzed from October 2004 to December 2016.Main outcomes and measuresLifetime suicide attempt and mental disorders in first-degree relatives, obtained through direct interviews or family history reports.ResultsThe study included 1119 adult probands (675 female [60.3%] and a mean [SD] age of 50 [12.0] years) and 5355 first-degree relatives (2752 female [51.4%] and a mean [SD] age of 52 [1.5] years). Of these participants, 90 (8.0%) of 1119 probands and 199 (3.7%) of 5355 relatives had a lifetime history of suicide attempt. Those with such a history had higher rates of all mental disorders, a greater number of disorders, and statistically significantly poorer current and lifetime global functioning. After adjustment for age and sex, a statistically significant association between suicide attempts in probands and in relatives was found at the NIMH site (OR, 2.6; 95% CI, 1.5-4.7), at the Lausanne site (OR, 3.1; 95% CI, 1.6-6.0), and in the combined data (OR, 2.9; 95% CI, 1.9-4.5). All mood disorder subtypes and substance use disorders were statistically significantly associated with suicide attempts. The familial association between lifetime suicide attempts in probands and relatives was not statistically significant for the combined sample (OR, 1.6; 95% CI, 1.0-2.7) after adjustment for comorbid conditions in probands and relatives. Social anxiety disorder in probands was associated with suicide attempts in relatives (OR, 2.4; 95% CI, 1.7-3.5) after controlling for comorbid mood, anxiety, and substance use disorders.Conclusions and relevanceFamiliality of suicide attempts appears to be explained by a history of mental disorders among those with suicide attempts; the novel finding of a common familial diathesis for suicide attempts and social anxiety, particularly in combination with mood disorders, has heuristic value for future research and may be a risk marker that can inform prevention efforts.

Project description:Suicidal behavior (SB) has a complex etiology of genes, environment or both. One of the genetic components in SB could be copy number variations (CNVs), since CNVs are implicated in a range of neurodevelopmental disorders. However, a recently published genome-wide and case-control study failed to observe a significant role of CNVs in SB (see E-MTAB-3519). Here we complement those initial observations by conducting a brief CNV-association study, for the first time in a family-based trio-sample with severe suicide attempt (SA) outcome in offspring (n=660 trios; the \GISS\ sample, see http://www.ncbi.nlm.nih.gov/pubmed/23422793 and refs therein). For association testing, we here used the FBAT-CNV methodology (http://www.ncbi.nlm.nih.gov/pubmed/18228561), which allows for CNV association testing directly on the raw intensity values (Illumina \log R ratio\), evaluating any type of CNVs (e.g. de novo or inherited) without reliance on CNV calling algorithms and robust to control selection biases. Here we have deposited these raw logR-values for 88,450 on-chip CNV-loci of the HumanOmni1-Quad_v1 chip, arranged in a standard pedigree format used as input for FBAT-CNV analysis in SVS software (goldenhelix.com): column 1 is the family ID, column 2 is the Subject type (1 = offspring, 2 = mother, 3 = father), column 3 is the father ID (? for missing), column 4 is the mother ID (? for missing), column 5 is the sex (1 = female, 0 = male), column 6 is the affection status (1 = suicide attempt, 0 = not affected) and columns 7 and onward are the logR-values for each CNV-loci as is listed in the header row. We observed experiment-wide significant association (P ≤ 5.6 x 10-7) of two proximal CNVs at chromosome 14 (Illumina markers cnvi0108946 and cnvi0118308, with NCBI 36.3 start positions 22794779 and 22582820). However, these CNV-associations mapped to T-cell receptor regions, and therefore most likely reflect inter-individual variation in somatic rearrangements occurring in white blood cells (as our source of DNA was blood), rather than association with SA. In conclusion, our results did not suggest any major role of CNVs in SA etiology, in line with the results of the recent case-control study (see E-MTAB-3519).

Project description:ImportanceApproximately one-third of US soldiers who attempt suicide have not received a mental health diagnosis (MH-Dx) before their suicide attempt (SA), yet little is known about risk factors for SA in those with no MH-Dx.ObjectiveTo examine whether premilitary mental health is associated with medically documented SA among US Army soldiers who do not receive an MH-Dx before their SA.Design, setting, and participantsThis cohort study used data from a representative survey of soldiers in the US Army entering basic combat training from April 1, 2011, to November 30, 2012, who were followed up via administrative records for the first 48 months of service. Analyses were conducted from April 5, 2021, to January 21, 2022. Regular Army enlisted soldiers (n = 21 772) recruited from 3 US Army installations during the first week of service who agreed to have their administrative records linked to their survey responses were included.ExposuresPreenlistment lifetime history of mental disorder, suicide ideation, SA, and nonsuicidal self-injury (NSSI) as reported during the baseline survey. Service-acquired MH-Dx and sociodemographic and service-related variables were identified using administrative records.Main outcomes and measuresDocumented SAs were identified using administrative medical records. Using a discrete-time survival framework, linear splines examined the pattern of SA risk over the first 48 months of service. Logistic regression analysis examined associations of lifetime baseline survey variables with subsequent, medically documented SA among soldiers who did vs did not receive an MH-Dx during service. Models were adjusted for time in service and sociodemographic and service-related variables.ResultsOf the 21 722 respondents (86.2% male, 20.4% Black, 61.8% White non-Hispanic), 253 made an SA in the first 48 months of service (male [75.4%]; Black [22.7%], White non-Hispanic [59.9%], or other race or ethnicity [17.4%]). Risk of SA peaked toward the end of the first year of service for both those who did and did not receive an MH-Dx during service. Of the 42.3% of individuals reporting at least 1 of the 4 baseline risk factors, 50.2% received an administrative MH-Dx during service vs 41.5% of those with none, and 1.6% had a documented SA vs 1.0% of those with none. Among individuals with no MH-Dx, medically documented SAs were associated with suicide ideation (odds ratio [OR], 2.2; 95% CI, 1.1-4.4), SA (OR, 11.3; 95% CI, 4.3-29.2), and NSSI (OR, 3.0; 95% CI, 1.3-6.8). For those who received an MH-Dx, medically documented SAs were associated with mental disorder (OR, 1.4; 95% CI, 1.0-1.9), SA (OR, 3.4; 95% CI, 2.1-5.6), and NSSI (OR, 1.8; 95% CI, 1.1-2.8). Interactions indicated the only explanatory variable that differed based on history of MH-Dx was preenlistment SA (χ21 = 4.7; P = .03), which had a larger OR among soldiers with no MH-Dx than among those with an MH-Dx.Conclusions and relevanceIn this study, the period of greatest SA risk and baseline risk factors for SA were similar in soldiers with and without an MH-Dx. This finding suggests that knowledge of the time course and preenlistment mental health factors can equally aid in identifying SA risk in soldiers who do and do not receive an MH-Dx.

Project description:BackgroundRates of suicide are increasing in the US. Although psychiatric disorders are associated with suicide risk, there is a dearth of epidemiological research on the relationship between suicide attempts (SAs) and eating disorders (EDs). The study therefore aimed to examine prevalence and correlates of SAs in DSM-5 EDs-anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED)-in a nationally representative sample of US adults. In addition, prevalence and correlates of SAs were examined in the two subtypes of AN-restricting (AN-R) and binge/purge (AN-BP) types.MethodsThe study included 36,171 respondents in the Third National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III) who completed structured diagnostic interviews (AUDADIS-5) and answered questions regarding SA histories and psychosocial impairment associated with EDs. We evaluated lifetime prevalence of SA, psychosocial impairment, clinical profiles, and psychiatric comorbidity in adults with EDs with and without SA histories, and temporal relationships between age onset of SA and EDs.ResultsPrevalence estimates of suicide attempts were 24.9% (for AN), 15.7% (for AN-R), 44.1% (for AN-BP), 31.4% (for BN), and 22.9% (for BED). Relative to respondents without specific EDs, adjusted odds ratios (AORs) of SAs were significantly greater in all EDs: AN = 5.40 (95% confidence intervals [CIs] = 3.80-7.67), AN-R = 3.16 (95% CIs = 1.82-5.42), AN-BP = 12.09 (95% CIs = 6.29-23.24), BN = 6.33 (95% CIs = 3.39-11.81), and BED = 4.83 (95% CIs = 3.54-6.60). Among those with SA history, mean age at first SA and number of SAs were not significantly different across the specific EDs. SA was associated with significantly earlier ED onset in BN and BED, longer duration of AN but shorter duration of BN, greater psychosocial impairment in AN and BN, and with significantly increased risk for psychiatric disorder comorbidity across EDs. Onset of BED was significantly more likely to precede SA (71.2%) but onsets of AN (50.4%) and BN (47.6%) were not.ConclusionsUS adults with lifetime DSM-5 EDs have significantly elevated risk of SA history. Even after adjusting for sociodemographic factors, those with lifetime EDs had a roughly 5-to-6-fold risk of SAs relative to those without specific EDs; the AN binge/purge type had an especially elevated risk of SAs. SA history was associated with distinctively different clinical profiles including greater risk for psychosocial impairment and psychiatric comorbidity. These findings highlight the importance of improving screening for EDs and for suicide histories.

Dataset Information

Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study.

Publications

Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets