Evaluation of the causal relationship between smoking and schizophrenia in East Asia.

Cigarette smoking has been suggested to be associated with the risk of schizophrenia in observational studies. A significant causal effect of smoking on schizophrenia has been reported in European populations using the Mendelian randomization approach; however, no evidence of causality was found in participants from East Asia. Using Taiwan Biobank (TWBB), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behaviors, including smoking initiation (N = 79,989) and the onset age (N = 15,582). We then meta-analyzed GWAS from TWBB and Biobank Japan (BBJ) with the total sample size of 245,425 for smoking initiation and 46,000 for onset age of smoking. The GWAS for schizophrenia was taken from the East Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample Mendelian randomization to estimate the causality of smoking behaviors on schizophrenia in East Asia. In TWBB, we identified one locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two loci for smoking initiation. In Mendelian randomization, genetically predicted smoking initiation (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89-18.01, P = 0.071) and onset age (OR for a per-year increase = 0.96, 95% CI = 0.91-1.01, P = 0.098) were not significantly associated with schizophrenia; the direction of effect was consistent with European Ancestry samples, which had higher statistical power. These findings provide tentative evidence consistent with a causal role of smoking on the development of schizophrenia in East Asian populations.

Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes.

AIMS/HYPOTHESIS: Psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD), are highly comorbid with type 2 diabetes. However, the mechanisms underlying such comorbidity are understudied. This study explored the familial aggregation of common psychiatric disorders and type 2 diabetes by testing family history association, and investigated the shared genetic loading between them by testing the polygenic risk score (PRS) association. METHODS: A total of 105,184 participants were recruited from the Taiwan Biobank, and genome-wide genotyping data were available for 95,238 participants. The Psychiatric Genomics Consortium-derived PRS for SCZ, MDD and BPD was calculated. Logistic regression was used to estimate the OR with CIs between a family history of SCZ/MDD/BPD and a family history of type 2 diabetes, and between the PRS and the risk of type 2 diabetes. RESULTS: A family history of type 2 diabetes was associated with a family history of SCZ (OR 1.23, 95% CI 1.08, 1.40), MDD (OR 1.19, 95% CI 1.13, 1.26) and BPD (OR 1.26, 95% CI 1.15, 1.39). Compared with paternal type 2 diabetes, maternal type 2 diabetes was associated with a higher risk of a family history of SCZ. SCZ PRS was negatively associated with type 2 diabetes in women (OR 0.92, 95% CI 0.88, 0.97), but not in men; the effect of SCZ PRS reduced after adjusting for BMI. MDD PRS was positively associated with type 2 diabetes (OR 1.04, 95% CI 1.00, 1.07); the effect of MDD PRS reduced after adjusting for BMI or smoking. BPD PRS was not associated with type 2 diabetes. CONCLUSIONS/INTERPRETATION: The comorbidity of type 2 diabetes with psychiatric disorders may be explained by shared familial factors. The shared polygenic loading between MDD and type 2 diabetes implies not only pleiotropy but also a shared genetic aetiology for the mechanism behind the comorbidity. The negative correlation between polygenic loading for SCZ and type 2 diabetes implies the role of environmental factors.

Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer.

Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, P = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, P = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, P = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, P = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression.

Association between polygenic liability for schizophrenia and substance involvement: A nationwide population-based study in Taiwan.

Schizophrenia and substance involvement frequently co-occur in individuals, and a bidirectional relationship between the two has been proposed; shared underlying genetic factors could be an alternative explanation. This study investigated the genetic overlap between schizophrenia and substance involvement, including tobacco, alcohol and betel nut use. The study subjects were recruited from the Taiwan Biobank, and genome-wide genotyping data was available for 18 327 participants without schizophrenia. We calculated the Psychiatric Genomics Consortium-derived polygenic risk score (PRS) for schizophrenia in each participant. The significance of the schizophrenia PRS associated with substance involvement was evaluated using a regression model with adjustments for gender, age and population stratification components. The modified effect of gender or birth decade was also explored. The schizophrenia PRS was positively associated with lifetime tobacco smoking in women (OR in per SD increase in PRS = 1.12 with 95% CI 1.04-1.20, P = .002), but not in men (OR = 0.99 with 95% CI 0.95-1.04, P = .74), and the gender-PRS interaction reached significance (P = .006). The OR between PRS and lifetime tobacco smoking increased with the birth decade (P of birth decade-PRS interaction = .0002). In women, OR increased from 0.97 (P = .85) for subjects with a birth decade before 1950 to 1.21 (P = .04) for subjects with a birth decade after 1980; in men, the corresponding OR increased from 0.88 (P = .04) to 1.13 (P = .11). There was no association between schizophrenia PRS and alcohol/betel nut use phenotypes. This study provides evidence for the genetic overlap between schizophrenia and tobacco use in women, and this overlap was stronger in the younger population.

Nonmedical prescription drug use of analgesics and sedatives/hypnotics in Taiwan: Results from the 2014 National Survey of Substance Use.

Nonmedical prescription drug use (NMPDU) has become a major public health issue but little is known in Asian populations. This study aimed to investigate the prevalence and correlates of NMPDU in Taiwan. Participants from the 2014 national survey of 17,837 individuals, aged 12 to 64 year, completed anonymously a computer-assisted self-interview. Past-year prescription drug use was divided into medical use only (MUO) and nonmedical use (NMU), defined as using the drug without a prescription, or more frequently, or in larger doses than prescribed. Problematic alcohol use was measured using the Alcohol Use Disorders Identification Test (AUDIT), problematic drug use using the 20-item Drug Abuse Screening Test (DAST), and depressive symptoms using the Center for Epidemiological Study-Depression (CES-D). The prevalence of past-year NMU was 3.02% for analgesics, 0.71% for sedatives/hypnotics, and 3.66% for either drug, with a very small overlap of NMU between analgesics and sedatives/hypnotics (0.07%). When individuals with NMU were compared to those without NMU (Non-NMU) and those with MUO, respectively, some correlates consistently identified, including young adulthood, tobacco smoking, alcohol drinking, and greater AUDIT's scores for analgesics, as well as hard drug use and greater DAST's scores for sedatives/hypnotics. NMU was associated with greater CES-D's scores for both analgesics and sedatives/hypnotics when compared to Non-NMU but not to MUO. Robust correlates of NMPDU could offer implications for development of prevention strategies of NMPDU.

E-Cigarette Use in a Country With Prevalent Tobacco Smoking: A Population-Based Study in Taiwan.

BACKGROUND: The different profiles of e-cigarette users in different age groups have seldom been investigated, particularly in populations facing a high prevalence of cigarette smoking. This study aims to examine the prevalence and correlates of e-cigarette use separately for adolescents and adults in nationally representative samples in Taiwan. METHODS: Among 17,837 participants in the 2014 National Survey of Substance Use in Taiwan, 4445 were aged 12 to 17 years and 13,392 were aged 18 to 64 years. Individuals' lifetime tobacco use was divided into four groups: non-use, exclusive e-cigarette use, exclusive cigarette use, and dual use. Questions on sociodemographic features, use and problematic use of tobacco, alcohol, and other drugs, and psychosocial distress, among others, were administered using a computer-assisted self-interview on tablet computers. RESULTS: Among lifetime users of e-cigarette (2.2% for adults and 0.8% for adolescents), 4.5% for adults and 36.6% for adolescents were exclusive e-cigarette users. From use of exclusive e-cigarettes to use of exclusive cigarettes to dual use, those usage groups were related to an increasing trend of adjusted odds ratios for use of other psychoactive substances, particularly problematic use of alcohol or drugs, and with more depressive symptoms. Two correlates were specific to e-cigarette use: alcohol use had stronger relationships with e-cigarette use among adolescents, and younger adults (18-34) were more likely to try e-cigarettes compared to older adults. CONCLUSIONS: These results provide essential information regarding e-cigarette use in the general population, and future prevention strategies should account for its specific correlates in young people.

Differences in prevalence, socio-behavioral correlates, and psychosocial distress between club drug and hard drug use in Taiwan: Results from the 2014 National Survey of Substance Use.

BACKGROUND: This study examined variation between users of 'club' and 'hard' drugs in Taiwan in terms of prevalence of use and demographics and psychosocial characteristics. METHODS: Data were derived from a survey of 17,837 Taiwanese civilians, aged 12-64 years, using stratified, multi-stage, random sampling. Participants completed a computer-assisted self-interview on tablet computers which covered use of legal substances, sedatives/hypnotics and prescription analgesics; use of illicit drugs/inhalants, risky sexual experiences; expectations of drugs; and psychological distress. FINDINGS: Approximately 1.29% of respondents reported ever using an illicit drug in their lifetime; prevalence estimates of club drugs (mainly ketamine, marijuana, and ecstasy) were slightly higher than hard drugs (mainly methamphetamine and heroin). Concurrent use of legal substances, particularly problematic use of alcohol and tobacco, as well as non-medical use of prescription drugs, were strong correlates of illicit drug use in general, with club drug use exhibiting an extremely strong association with alcohol use. Club drug users were demographically different from hard drug users, including in terms of their gender, age, and level of educational attainment. They were also more likely to be divorced or widowed, to report risky sexual partnerships and more depressive symptoms than hard drug users. CONCLUSIONS: Our findings indicate drug type specific distinct psychosocial characteristics, which may warrant further attention in the design of treatment and intervention programs.