Trait similarities between spouses are a key factor that shapes the landscape of complex human traits. The driving force behind the spousal correlations can increase the overall prevalence of disorders, influence occurrences of comorbidities and bias estimations of genetic architectures. However, there is a lack of large-scale studies examining cultural differences and generational trends in spousal correlations for psychiatric disorders.
View Article and Find Full Text PDFBehav Genet
August 2025
Whether education modifies genetic influences on cognition has not been fully explored, especially in non-European populations. Using the older adult cohort from the Taiwan Biobank of East Asian populations, this study aimed to investigate the modifying effect of education on the association of the apolipoprotein E (APOE) ε4 allele and polygenic scores (PGS) for Alzheimer's disease (PGS), cognitive performance (PGS), education attainment (PGS), and schizophrenia (PGS) with cognitive ability. Participants aged > 60 years were included in this cohort study.
View Article and Find Full Text PDFPsychol Med
August 2025
Background: Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods: We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results: We replicated the well-known association at the locus (lead single-nucleotide polymorphism [SNP]: rs147144681, = 1.
Substance use has been associated with differences in adult brain morphology; however, it is unclear whether these differences precede or are a result of substance use substance use. We investigated the impact of polygenic risk scores (PRSs) for cannabis use disorder (CUD) and general substance use and substance use disorder liability (SU/SUD) on brain morphology in drug-naïve adolescents. Baseline data were used from 1874 European-descent participants (ages 9-11) comprising 222, 328 and 387 pairs of MZ twins, DZ twins, and Non-Twin Siblings, respectively, in the Adolescent Brain Cognitive Development Study.
View Article and Find Full Text PDFSubstance use has been associated with differences in adult brain morphology; however, it is unclear whether these differences precede or are a result of substance use substance use. We investigated the impact of polygenic risk scores (PRSs) for cannabis use disorder (CUD) and general substance use and substance use disorder liability (SU/SUD) on brain morphology in drug-naïve adolescents. Baseline data were used from 1,874 European-descent participants (ages 9-11) comprising 222, 328 and 387 pairs of MZ twins, DZ twins, and Non-Twin Siblings, respectively, in the Adolescent Brain Cognitive Development Study.
View Article and Find Full Text PDFAnn Gen Psychiatry
April 2025
Background: Genetic susceptibility to mental health and cognitive traits, as well as air pollution, significantly impact cognition. The interplay between polygenic liability and fine particulate matter (PM) remains unclear due to the limited number of large-scale studies in Asia. This study utilized the Taiwan Biobank, a nationwide community-based database, to investigate the main and modified effect of PM on individuals' polygenic susceptibility in cognition.
View Article and Find Full Text PDFBiol Psychiatry
September 2025
Background: In this study, we investigated the interplay between molecular measures of polygenic risk scores (PRSs) and conventional measures of family history (FH) on the risk of 4 psychiatric disorders: schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD) in community samples of East Asian populations. We examined the individual and joint associations and the relative contributions of PRS and FH and evaluated the potential of combining transdiagnostic PRSs and FHs to improve risk prediction.
Methods: The genotyping of 106,581 unrelated participants from the Taiwan Biobank was linked to the National Health Insurance Research Database to retrieve information on ICD-defined diseases and FH.
medRxiv
February 2025
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. We conducted a genome-wide association study of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry, 10,231 of African ancestry, 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes. We replicated the well-known association at the locus (lead SNP: rs147144681, p =1.
View Article and Find Full Text PDFBipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.
View Article and Find Full Text PDFSubstance use and substance use disorders run in families. While it has long been recognized that the etiology of substance use behaviors and disorders involves a combination of genetic and environmental factors, two key questions remain largely unanswered: (1) the intergenerational transmission through which these genetic predispositions are passed from parents to children, and (2) the molecular mechanisms linking genetic variants to substance use behaviors and disorders. This article aims to provide a comprehensive conceptual framework and methodological approach for investigating the intergenerational transmission of substance use behaviors and disorders, by integrating genetic nurture analysis, gene expression imputation, and weighted gene co-expression network analysis.
View Article and Find Full Text PDFThe mechanism underlying the co-occurrence of major depressive disorder (MDD) and gynecological diseases remains unclear. This study aimed to investigate the familial co-aggregation and shared genetic loading between MDD and gynecological diseases, namely dysmenorrhea, endometriosis, uterine leiomyomas (UL), and polycystic ovary syndrome (PCOS). Overall, 2,121,632 females born 1970-1999 with parental information were enrolled from the Taiwan National Health Insurance Research Database (NHIRD); 25,142 same-sex twins and 951,779 persons with full-sibling(s) were selected.
View Article and Find Full Text PDFEmerging evidence has shown that assortative mating (AM) is a key factor that shapes the landscape of complex human traits. It can increase the overall prevalence of disorders, influence occurrences of comorbidities, and bias estimation of genetic architectures. However, there is lack of large-scale studies to examine the cultural differences and the generational trends of AM for psychiatric disorders.
View Article and Find Full Text PDFBackground: It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear.
Methods: This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970-1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled.
Am J Med Genet B Neuropsychiatr Genet
January 2025
To comprehensively investigate the risk factors associated with depression, traditional Chinese medicine constitution (TCMC) has been found to be related to depression. However, the underlying mechanism remains unclear. This study examined the association between the concept of unbalanced TCMCs and major depressive disorder (MDD), investigated the overlapping polygenic risks between unbalanced TCMC and MDD, and performed a mediation test to establish potential pathways.
View Article and Find Full Text PDFObjectives: To assess the causal influence of sleep and circadian traits on coronary artery disease and sudden cardiac arrest with adjustment for obesity through a two-sample Mendelian randomization study.
Methods: We used summary statistics of 5 sleep and circadian traits for genome-wide association studies, including chronotype, sleep duration, long sleep (≥9 h a day), short sleep (<7 h a day), and insomnia (sample size range: 237,622-651,295). Coronary artery disease genome-wide association studies with 60,801 cases and 123,504 controls, sudden cardiac arrest genome-wide association studies with 3939 cases and 25,989 controls, and obesity genome-wide association studies with 806,834 individuals were also used.
Major depressive disorder (MDD) is associated with high heterogeneity in clinical presentation. In addition, response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably among patients. Therefore, identifying genetic variants that may contribute to SSRI treatment responses in MDD is essential.
View Article and Find Full Text PDFJ Affect Disord
January 2023
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.
Schizophrenia (Heidelb)
September 2022
Int J Obes (Lond)
August 2022
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.
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.
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