Genome-wide meta-analysis of alcohol use disorder in East Asians.

Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. Genome-wide association studies (GWAS) have identified ~30 AUD risk genes in European populations, but many fewer in East Asians. We conducted GWAS and genome-wide meta-analysis of AUD in 13,551 subjects with East Asian ancestry, using published summary data and newly genotyped data from five cohorts: (1) electronic health record (EHR)-diagnosed AUD in the Million Veteran Program (MVP) sample; (2) DSM-IV diagnosed alcohol dependence (AD) in a Han Chinese-GSA (array) cohort; (3) AD in a Han Chinese-Cyto (array) cohort; and (4) two AD Thai cohorts. The MVP and Thai samples included newly genotyped subjects from ongoing recruitment. In total, 2254 cases and 11,297 controls were analyzed. An AUD polygenic risk score was analyzed in an independent sample with 4464 East Asians (Genetic Epidemiology Research in Adult Health and Aging (GERA)). Phenotypes from survey data and ICD-9-CM diagnoses were tested for association with the AUD PRS. Two risk loci were detected: the well-known functional variant rs1229984 in ADH1B and rs3782886 in BRAP (near the ALDH2 gene locus) are the lead variants. AUD PRS was significantly associated with days per week of alcohol consumption (beta = 0.43, SE = 0.067, p = 2.47 × 10-10) and nominally associated with pack years of smoking (beta = 0.09, SE = 0.05, p = 4.52 × 10-2) and ever vs. never smoking (beta = 0.06, SE = 0.02, p = 1.14 × 10-2). This is the largest GWAS of AUD in East Asians to date. Building on previous findings, we were able to analyze pleiotropy, but did not identify any new risk regions, underscoring the importance of recruiting additional East Asian subjects for alcohol GWAS.

A risk-scoring scheme for suicide attempts among patients with bipolar disorder in a Thai patient cohort.

BACKGROUND: In Thailand, risk factors associated with suicide attempts in bipolar disorder (BD) are rarely investigated, nor has a specific risk-scoring scheme to assist in the identification of BD patients at risk for attempting suicide been proposed. OBJECTIVE: To develop a simple risk-scoring scheme to identify patients with BD who may be at risk for attempting suicide. METHODS: Medical files of 489 patients diagnosed with BD at Suanprung Psychiatric Hospital between October 2006 and May 2009 were reviewed. Cases included BD patients hospitalized due to attempted suicide (n = 58), and seven controls were selected (per suicide case) among BD in- and out-patients who did not attempt suicide, with patients being visited the same day or within 1 week of case study (n = 431). Broad sociodemographic and clinical factors were gathered and analyzed using multivariate logistic regression, to obtain a set of risk factors. Scores for each indicator were weighted, assigned, and summed to create a total risk score, which was divided into low, moderate, and high-risk suicide attempt groups. RESULTS: Six statistically significant indicators associated with suicide attempts were included in the risk-scoring scheme: depression, psychotic symptom(s), number of previous suicide attempts, stressful life event(s), medication adherence, and BD treatment years. A total risk score (possible range -1.5 to 11.5) explained an 88.6% probability of suicide attempts based on the receiver operating characteristic (ROC) analysis. Likelihood ratios of suicide attempts with low risk scores (below 2.5), moderate risk scores (2.5-8.0), and high risk scores (above 8.0) were 0.11 (95% CI 0.04-0.32), 1.72 (95% CI 1.41-2.10), and 19.0 (95% CI 6.17-58.16), respectively. CONCLUSION: The proposed risk-scoring scheme is BD-specific, comprising six key indicators for simple, routine assessment and classification of patients to three risk groups. Further validation is required before adopting this scheme in other clinical settings.

Factors related to suicide attempts among individuals with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is the leading cause of suicidal behaviors. Risk related to suicide attempts among individuals with MDD remains uninvestigated in upper northern Thailand, where the completed suicide rate is the highest in the nation. OBJECTIVE: To examine risk related to suicide attempts among individuals with MDD. METHODS: Individuals diagnosed with MDD using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), codes F32.x and F33.x, seeking care at Suanprung Psychiatric Hospital between October 2006 and May 2009 were eligible. All individuals with MDD admitted due to suicide attempts were defined as cases (n = 186), and four controls per case were selected from those who did not attempt suicide on the same day or within a week of case selection (n = 914). Their medical charts were reviewed for sociodemographic and clinical factors influencing suicide attempts using multivariable logistic regression analysis. RESULTS: Factors related to suicide attempts were stressful life events (adjusted odds ratio [OR], 2.32; 95% confidence interval [CI]: 1.27-4.24), alcohol use (adjusted OR, 2.08; 95% CI: 1.29-3.34), intermittent or poor psychiatric medications adherence (adjusted OR, 2.25; 95% CI: 1.44-3.51), up to two previous suicide attempts (adjusted OR, 3.64; 95% CI: 2.32-5.71), more than two previous suicide attempts (adjusted OR, 11.47; 95% CI: 5.73-22.95), and prescribed antipsychotics (adjusted OR, 3.84; 95% CI: 2.48-5.95). Risk factors that were inversely related to suicide attempts were increasing years of MDD treatment; one to five years (adjusted OR, 0.22; 95% CI: 0.11-0.44), over five years (adjusted OR, 0.44; 95% CI: 0.23-0.86), and antidepressant prescribed (norepinephrine [NE] and/or serotonin reuptake inhibitors [SRIs], adjusted OR, 0.28; 95% CI: 0.10-0.78). The final model explained 85.8% probability of suicide attempts. CONCLUSION: Seven key factors suggested from this study may facilitate clinicians to identify individuals with MDD at risk of suicide attempt and provide them close monitoring, timely assessment, and intensive treatments.

Inter-rater reliability and concurrent validity of DSM-IV opioid dependence in a Hmong isolate using the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA).

Because isolated populations offer relative genetic and environmental homogeneity, they are important resources for mapping genes for complex traits. Reliable and valid phenotypic characterization of the disease in the population studied is essential. We examined diagnostic reliability and concurrent validity of DSM-IV opioid dependence (OD) in a Hmong population in Thailand with historically high rates of opium (and heroin) use. 578 Thai-speaking Hmong individuals were assessed for lifetime OD, using Thai versions of both the Semi-Structured Assessment for Drug Dependence and Alcoholism (Thai SSADDA) and the Mini-Neuropsychiatric Interview (Thai MINI; adapted for lifetime diagnoses). In a subsample of 123 individuals, two raters interviewed each subject independently within a 2-week period. Chance-corrected agreement on the OD diagnosis was assessed between raters and instruments. Results showed excellent agreement for the DSM-IV diagnosis of OD both for the SSADDA (κ=0.97) and MINI (κ=1.00) and between the SSADDA and MINI (κ=0.97). Consistent with reliability assessments of English versions, our data demonstrate high reliability for Thai versions of the SSADDA and MINI in the diagnosis of OD. The high concordance between instruments supports the concurrent validity of the diagnosis. Either interview provides reliable, valid OD diagnoses in Thai-speaking Hmong individuals.

Incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients.

BACKGROUND: The incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients remain uninvestigated in Thailand. OBJECTIVE: To determine incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients. METHODS: A retrospective cohort study was conducted by reviewing medical charts at Suanprung Psychiatric Hospital, Chiang Mai, Thailand. Mood disorder patients, diagnosed with the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes F31.x, F32.x, and F33.x, who were admitted owing to suicide attempts between October 2006 and May 2009 were eligible. The influence of sociodemographic and clinical risk factors on suicide reattempts was investigated using Cox's proportional-hazards regression analysis. RESULTS: Of 235 eligible mood disorder patients, 36 (15.3%) reattempted suicide (median 109.5 days, range 1-322), seven (3.0%) completed suicide (median 90 days, range 5-185), and 192 (84.2%) neither reattempted nor completed suicide during follow-up. Of all nonfatal suicide reattempts, 14 patients (38.9%) did so within 90 days. Among suicide completers, one (14.3%) did so 5 days after discharge, and four (57.1%) did so within 90 days. The following three risk factors explained 73.3% of the probability of suicide reattempts: over two previous suicide attempts before the index admission (adjusted hazard ratio [HR] 2.48; 95% confidence interval [CI] 1.07-5.76), being concomitantly prescribed typical and atypical antipsychotics (adjusted HR 4.79; 95% CI 1.39-16.52) and antidepressants, and taking a selective serotonin reuptake inhibitor alone (adjusted HR 5.08; 95% CI 1.14-22.75) or concomitantly with norepinephrine and/or serotonin reuptake inhibitors (adjusted HR 6.18; 95% CI 1.13-33.65). CONCLUSION: Approximately 40% of suicide reattempts in mood disorder patients occurred within 90 days after psychiatric hospital discharge. For mood disorders and when there have been over two previous suicide attempts, prescribed antipsychotics or antidepressants may help predict suicide reattempts.

Demographic changes and marker properties affect detection of human population differentiation.

BACKGROUND: Differentiating genetically between populations is valuable for admixture and population stratification detection and in understanding population history. This is easy to achieve for major continental populations, but not for closely related populations. It has been claimed that a large marker panel is necessary to reliably distinguish populations within a continent. We investigated whether empirical genetic differentiation could be accomplished efficiently among three Asian populations (Hmong, Thai, and Chinese) using a small set of highly variable markers (15 tetranucleotide and 17 dinucleotide repeats). RESULTS: Hmong could be differentiated from Thai and Chinese based on multi-locus genotypes, but Thai and Chinese were indistinguishable from each other. We found significant evidence for a recent population bottleneck followed by expansion in the Hmong that was not present in the Thai or Chinese. Tetranucleotide repeats were less useful than dinucleotide repeat markers in distinguishing between major continental populations (Asian, European, and African) while both successfully distinguished Hmong from Thai and Chinese. CONCLUSION: Demographic history contributes significantly to robust detection of intracontinental population structure. Populations having experienced a rapid size reduction may be reliably distinguished as a result of a genetic drift -driven redistribution of population allele frequencies. Tetranucleotide markers, which differ from dinucleotide markers in mutation mechanism and rate, are similar in information content to dinucleotide markers in this situation. These factors should be considered when identifying populations suitable for gene mapping studies and when interpreting interpopulation relationships based on microsatellite markers.