The use of premixed drugs in commodity packets in the population: prevalence and correlates revealed by the 2018 National Survey of Substance Use in Taiwan.

BACKGROUND: Administering premixed drugs in commodity packets was first reported in Asia in 2015, but there continues to be a dearth of related population-based data. This study aimed at examining (1) the prevalence of drug packet use in the population and (2) the sociodemographic profiles, particularly gender distribution, of drug packet users. METHODS: Data were derived from a survey of 18,626 Taiwanese civilians, aged 12-64 years, using stratified, multi-stage, random sampling in 2018. Participants anonymously completed a computer-assisted self-interview on tablet computers which covered the use and problematic use of illicit drugs/inhalants, prescription drugs and other psychoactive substances, among others. RESULTS: Approximately 1.46% of respondents had a lifetime use of illicit drugs, with drugs in commodity packets (0.18%) being ranked the fifth-most commonly used illicit drugs, higher than nitrous oxide (0.14%) and heroin (0.09%). Ten formats of drug packets were endorsed by users. Approximately 81.6% of persons with drug packet use had a lifetime use of other illicit drugs. The correlates of the use of drugs in commodity packets were similar to those of the exclusive use of other drugs except that there was a lack of gender differences in the use of drugs in commodity packets but not in the exclusive use of other drugs. CONCLUSION: Drugs in commodity packets have become a common way of administering illicit drugs in the population in Taiwan, and there were no gender differences among users. Our findings have implications for more efficient drug testing and culturally appropriate intervention for drug packet use.

Associations of polygenic risks, depression, and obesity-related traits in Taiwan Biobank.

BACKGROUND: The comorbidity of obesity and major depressive disorder (MDD) may be attributable to a bidirectional relationship and shared genetic influence. We aimed to examine the polygenic associations between obesity and MDD and to characterize their corresponding impacts on the obesity mechanism. METHODS: Genome-wide genotyping was available in 106,604 unrelated individuals from Taiwan Biobank. Polygenic risk score (PRS) for body mass index (BMI) and MDD was derived to evaluate their effects on obesity-related traits. Stratified analyses were performed for the modified effect of depression on the polygenic associations. RESULTS: The MDD PRS was positively associated with waistline (beta in per SD increase in PRS = 0.12), hipline (beta = 0.08), waist-hip ratio (WHR) (beta = 0.05), body fat rate (beta = 0.08), BMI (beta = 0.05), overweight (OR = 1.02 for BMI ≥ 25), and obesity (OR = 1.05 for BMI ≥ 30). For the synergism between depression and BMI PRS, the presence of active depression symptoms defined by the PHQ-4 (p for interaction < 0.05 for waistline, WHR, and BMI) was more salient than lifetime MDD. LIMITATIONS: Limitations include recall bias for MDD due to a retrospective self-reporting questionnaire, a low response rate of the PHQ-4 for evaluating active psychological symptoms, and limited generalizability to non-Taiwanese ancestries. CONCLUSIONS: The shared genetic etiology of obesity and depression was demonstrated. The amplified effect of BMI polygenic effect on obesity for individuals with active depressive symptoms was also characterized. The study may be helpful for designing public health interventions to reduce the disease burden caused by obesity and depression.

The association of personality polygenic risk score, psychosocial protective factors and suicide attempt in mood disorder.

Some personality traits, especially neuroticism, has been found to be associated with suicide attempt (SA) in mood disorder patients. The present study explored the association between personality traits and SA using polygenic risk scores (PRS) for personality among patients with mood disorders. We also investigated the effects of a variety of psychosocial variables on SA. Patients with bipolar disorder (BPD, N = 841) and major depressive disorder (MDD, N = 710) were recruited from hospitals in Taiwan. Lifetime SA and information on psychosocial factors was collected. We calculated the PRS of neuroticism and extraversion. A trend test for SA was performed across quartiles of the PRS for neuroticism and extraversion, and logistic regression analyses were performed to examine the associations between psychosocial factors and SA, accounting for the PRS of personality traits. The prevalence of SA was higher in MDD than in BPD patients. The risk of SA was elevated in MDD patients with a higher quintile of PRS in neuroticism and a lower quintile of PRS in extraversion. The multiple regression analysis results demonstrated that later age of onset, higher family support and resilience, and lower overall social support were protective factors against SA. From the perspective of suicide prevention efforts, strengthening family support and conducting resilience training for patients with mood disorders may be beneficial interventions in clinical settings.

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.

Niacin skin flush and membrane polyunsaturated fatty acids in schizophrenia from the acute state to partial remission: a dynamic relationship.

Despite the consistent finding of an attenuated niacin-induced flush response in schizophrenia, its long-term stability and relationship to the membrane polyunsaturated fatty acid (PUFA) levels remain unknown. We conducted niacin skin tests and measured the membrane PUFAs using gas chromatography among 46 schizophrenia inpatients and 37 healthy controls at the baseline and the 2-month follow-up. Attenuated flush responses were persistently observed in schizophrenia patients in both acute and partial remission states, whereas an increased flush response was found in the controls. A persistent decrease in both dihomo-gamma-linolenic acid and docosahexaenoic acid and an increased turnover of arachidonic acid (ARA) via endogenous biosynthesis were found in schizophrenia patients. A composite niacin flush score by combining those with a control-to-case ratio of >1.4 (i.e., scores at 5 min of 0.1 M, 0.01 M, and 0.001 M + 10 min of 0.01 M and 0.001 M + 15 min of 0.001 M) at the baseline was correlated positively with ARA levels among controls but not among schizophrenia patients, whereas the flush score at the 2-month follow-up was correlated positively with ARA levels among patients. The 2-month persistence of attenuated niacin-induced flush response in schizophrenia patients implies that the niacin skin test might tap a long-term vulnerability to schizophrenia beyond acute exacerbation.

Causality of abdominal obesity on cognition: a trans-ethnic Mendelian randomization study.

BACKGROUND: Obesity has been associated with cognition in observational studies; however, whether its effect is confounding or a reverse causality remains inconclusive. This study aimed to investigate the causal relationships of overall obesity, measured by body mass index (BMI), and abdominal adiposity, measured by waist-hip ratio adjusted for BMI (WHRadjBMI), and cognition across European and Asian populations using Mendelian randomization (MR) analysis. METHODS: We used publicly available genome-wide association study (GWAS) summary data of European ancestry, including BMI (n = 322,154) and WHRadjBMI (n = 210,088) from the GIANT consortium, and cognition performance (n = 257,828) from the UK Biobank and COGENT consortium. Data for individuals of Asian ancestry were retrieved from Taiwan Biobank to perform GWAS for BMI (n = 65,689), WHRadjBMI (n = 65,683), and Mini-Mental State Examination (MMSE, n = 21,273). MR analysis was carried out using the inverse-variance weighted method for the main results. Further, we examined the overall pleiotropy by MR-Egger intercept, and detected and adjusted for possible outliers using MR PRESSO. RESULTS: No causal effect of BMI on cognition performance (beta [95% CI] = 0.00 [-0.07, 0.07], p value = 0.91) was found for Europeans; however, a 1-SD increase in WHRadjBMI was associated with a 0.07 standardized score decrease in cognition performance (beta [95% CI] = -0.07 [-0.12, -0.02], p value = 0.006). Further, no causal effect of BMI on MMSE (beta [95% CI] = 0.01 [-0.08, 0.10], p = 0.91) was found for Asians; however, a 1-SD increase in WHRadjBMI was associated with a 0.17 standardized score decrease in MMSE (beta [95% CI] = -0.17 [-0.30, -0.03], p = 0.02). In both populations, overall pleiotropy was not detected, and outliers did not affect the robustness of the main findings. CONCLUSIONS: This trans-ethnic MR study reveals that abdominal adiposity, as measured by WHR adjusted for BMI, impairs cognition, whereas weak evidence suggests that BMI impairs cognition.

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.

Men's decrease and women's increase in harmful alcohol use from the 2014 to 2018 national surveys in Taiwan: A harbinger for an emerging national trend in East Asia?

BACKGROUND: Gender differences in alcohol use have narrowed in Western societies, but that in Asia has been less investigated. By comparing the 2014 and 2018 waves of the national survey in Taiwan, we aimed to examine the gender differences in population trends in past-month alcohol use, binge drinking, and harmful alcohol use. METHODS: The national survey enrolled 17,837 participants in 2014 and 18,626 participants in 2018. Binge drinking was defined as having ≥5 drinks on one occasion in the past month, and harmful alcohol use as having an Alcohol Use Disorders Identification Test score of ≥8. RESULTS: There were significant decreases from 2014 to 2018 in the population's prevalence of past-month alcohol use, binge drinking, and harmful alcohol use. However, males and females had different trends: males showed significant reductions in all three alcohol use behaviours (a decrease of 3.79%, 1.59%, and 2.60%, respectively), while females exhibited a significant rise in harmful alcohol use (from 1.32% to 1.72%), particularly among those aged 18-29 years. CONCLUSION: There was gender convergence in alcohol use in Taiwan, mainly due to men's decrease and women's increase in harmful alcohol use. Our findings have important implications for the intervention and prevention of the problematic use of alcohol in East Asia.

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.

Advanced Paternal Age and Early Onset of Schizophrenia in Sporadic Cases: Not Confounded by Parental Polygenic Risk for Schizophrenia.

BACKGROUND: Whether paternal age effect on schizophrenia is a causation or just an association due to confounding by selection into late parenthood is still debated. We investigated the association between paternal age and early onset of schizophrenia in offspring, controlling for both paternal and maternal predisposition to schizophrenia as empirically estimated using polygenic risk score (PRS) derived from the Psychiatric Genomics Consortium. METHODS: Among 2923 sporadic schizophrenia cases selected from the Schizophrenia Trio Genomic Research in Taiwan project, 1649 had parents' genotyping data. The relationships of paternal schizophrenia PRS to paternal age at first birth (AFB) and of maternal schizophrenia PRS to maternal AFB were examined. A logistic regression model of patients' early onset of schizophrenia (≤18 years old) on paternal age was conducted. RESULTS: Advanced paternal age over 20 years exhibited a trend of an increasing proportion of early onset of schizophrenia (odds ratio per 10-year increase in paternal age = 1.28, p = .007) after adjusting for maternal age, sex, and age. Older paternal AFB also exhibited an increasing trend of paternal schizophrenia PRS. Additionally, a U-shaped relationship between maternal AFB and maternal schizophrenia PRS was observed. After adjusting for both paternal and maternal schizophrenia PRS, the association of paternal age with patients' early onset of schizophrenia remained (odds ratio = 1.29, p = .04). CONCLUSIONS: The association between paternal age and early onset of schizophrenia was not confounded by parental PRS for schizophrenia, which partially captures parental genetic vulnerability to schizophrenia. Our findings support an independent role of paternal age per se in increased risk of early onset of schizophrenia in offspring.

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.

Genetic loci associated with an earlier age at onset in multiplex schizophrenia.

An earlier age at onset (AAO) has been associated with greater genetic loadings in schizophrenia. This study aimed to identify modifier loci associated with an earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was conducted in 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores (GRS) composed of the candidate loci were used to distinguish patients with an early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands. When 132 patients with an earlier AAO and 158 patients with a later AAO were included, a significant trend in the 14-SNP GRS was detected among those unrelated probands from 4 family groups with the earliest, earlier, later, and latest AAO. The overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co-affected siblings of the GWAS probands and trend effect across unrelated patients. Preliminary network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson's disease and schizophrenia research.

Handedness and schizotypy: The potential effect of changing the writing-hand.

Mixed-handedness, which has been associated with schizotypy in recent studies, might exist for at least two different reasons: it is innate or it has been forced. We examined whether the association between mixed-handedness and schizotypy differs depending on its source. We enrolled 3485 college students in Taiwan. We used both the Perceptual Aberration Scale and Schizotypal Personality Questionnaire to assess schizotypy, and the Annett Hand Preference Questionnaire to assess handedness. Two ways of classifying handedness were examined: the three-way classification based on Annett's categories and mixed- vs. non-mixed-handedness based on Degree of Handedness. Both mixed-handedness groups showed higher positive schizotypy scores. Among mixed handers, those who had been required to change their writing hand from left to right had higher positive schizotypy scores. Being forced to change writing hand seemed to be related to a higher level of schizotypy. The potential effect of the social pressure against using the left hand for writing is discussed.

Estimation of heritability for varied indexes of handedness.

Inconsistent results of the molecular studies for handedness have been reported. One of the key issues involved could be ways of assessing handedness. The current study aimed to identify the index of handedness better reveal the genetic component, which showed higher heritability. We measured handedness using the Annett's handedness questionnaire. The college students participating in this study filled the questionnaire in the class while their first-degree relatives returned questionnaires one to two weeks later. A total of 1,968 subjects returned their questionnaires, including 640 college students and 1,328 first-degree relatives. Among the 449 college students returning at least one handedness questionnaire for their parents, a total of 449 fathers, 440 mothers, and 425 siblings participated in the study. The index of mixed-handedness (e.g., Degree of Handedness) showed highest heritability (0.67), followed by the Hand Preference Index (0.52), and then the Direction of Handedness (0.39). Using an index of mixed-handedness for future molecular studies was suggested.

Inference of cross-level interaction between genes and contextual factors in a matched case-control metabolic syndrome study: a Bayesian approach.

Genes, environment, and the interaction between them are each known to play an important role in the risk for developing complex diseases such as metabolic syndrome. For environmental factors, most studies focused on the measurements observed at the individual level, and therefore can only consider the gene-environment interaction at the same individual scale. Indeed the group-level (called contextual) environmental variables, such as community factors and the degree of local area development, may modify the genetic effect as well. To examine such cross-level interaction between genes and contextual factors, a flexible statistical model quantifying the variability of the genetic effects across different categories of the contextual variable is in need. With a Bayesian generalized linear mixed-effects model with an unconditional likelihood, we investigate whether the individual genetic effect is modified by the group-level residential environment factor in a matched case-control metabolic syndrome study. Such cross-level interaction is evaluated by examining the heterogeneity in allelic effects under various contextual categories, based on posterior samples from Markov chain Monte Carlo methods. The Bayesian analysis indicates that the effect of rs1801282 on metabolic syndrome development is modified by the contextual environmental factor. That is, even among individuals with the same genetic component of PPARG_Pro12Ala, living in a residential area with low availability of exercise facilities may result in higher risk. The modification of the group-level environment factors on the individual genetic attributes can be essential, and this Bayesian model is able to provide a quantitative assessment for such cross-level interaction. The Bayesian inference based on the full likelihood is flexible with any phenotype, and easy to implement computationally. This model has a wide applicability and may help unravel the complexity in development of complex diseases.

The cross-cultural nature of the relationship between schizotypy and mixed-handedness.

Positive schizotypy is associated with non-right-handedness, which includes left- and mixed-handedness. However, because the underlying mechanisms might be different, it is important to examine whether both left- and mixed-handedness are associated with a high incidence of schizotypy. During 2009-2010, we used both the Perceptual Aberration Scale and Schizotypal Personality Questionnaire to assess 1315 undergraduate students in Taiwan for schizotypy and the Annett handedness questionnaire to assess handedness. Among the three-way classifications based on Annett's grouping, the fully left-handed group appeared to have the lowest score of positive schizotypy; next was the fully right-handed group and then the mixed-handed. Among the three-way classifications driven from cluster analysis, mixed-handers showed highest score of positive schizotypy. When handedness was treated continuously, both direction (e.g., Hand Preference Index) and consistency (e.g., Either hand use score) indicators were significantly correlated with schizotypy. The results of regression analyses showed that the quadratic handedness measure were negatively associated with schizotypy. The results remained similar after correcting for social pressure on left-handedness. In conclusion, the relationship between schizotypy and mixed-handedness appears to be cross-cultural. The dichotomous classification of handedness, right- vs. non-right-handedness, appears to be insufficient. Additional studies on the distinct mechanisms of mixed- and left-handedness are warranted.

Performance on the Wisconsin Card Sorting Test in families of schizophrenia patients with different familial loadings.

Despite the consistent presence of performance deficits on the Wisconsin Card Sorting Test (WCST) in schizophrenia patients, whether poorer performance is also present in their nonpsychotic relatives is not certain. This study aimed to estimate both the recurrence risk ratio (λs) and the heritability of WCST scores in simplex and multiplex families, respectively, and to examine the influence of familial loading on these estimates. Participants were patients with schizophrenia and their nonpsychotic first-degree relatives from 168 simplex families and 653 multiplex families as well as 440 normal comparisons. On the basis of adjusted z scores, both the λs at a series of cutoff points and heritability estimates based on variance component modeling in the nonpsychotic relatives of schizophrenia patients were estimated. The WCST deficits in schizophrenia patients were more prominent in multiplex families than in simplex ones. Among relatives, WCST deficits were limited to parents of multiplex families for most WCST scores and siblings from multiplex families for total errors, perseverative responses, and perseverative errors. Pertaining to λs, the estimates for multiplex families (highest estimates ranging from 7.9 to 11.0) were greater than those for simplex ones (<2.5). Nevertheless, the heritability estimates were very similar between simplex (ranging from 0% to 17%) and multiplex (ranging from 0% to 21%) families, with the latter having slightly greater values than the former. There is only a small-to-modest familial aggregation on part of WCST scores in families of schizophrenia patients, and this may limit its use as endophenotypic markers to schizophrenia susceptibility.