Genome-wide association study of borderline personality disorder identifies 11 loci and highlights shared risk with mental and somatic disorders.

We conducted the largest genome-wide meta-analysis of borderline personality disorder (BPD) to date, with a discovery sample of 12,339 cases and 1,041,717 controls, and a replication study of 685 cases and 107,750 controls (all participants of European ancestry). We identified 11 independent associated genomic loci, and nine risk genes in the gene-based analysis. We observed a single-nucleotide polymorphism (SNP) heritability of 17.

Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.

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.

Protein Associations With Alcohol Consumption and Genetic Risk for Alcohol-Related Sociomedical Conditions.

Studies investigating proteomic associations with alcohol consumption and the genetic links of these proteins to alcohol-related traits are scarce. The aims of our study were (1) to identify proteins associated with alcohol consumption and (2) to investigate the molecular pathways and genetics linking the identified proteins to alcohol consumption and related sociomedical conditions. We generated proteomic and genotypic data from blood samples of 387 Finnish twins (age range: 56-70) and calculated polygenic risk scores (PRSs) of eight alcohol-related traits: obesity, alcohol dependence, number of drinks per week, number of cigarettes per day, major depressive disorders (MDDs), schizophrenia, externalising behaviour and educational attainment.

Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes.

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes, but these variants have proven challenging to detect. Genome-wide association studies of monozygotic twin differences are conducted through family-based variance analyses, which are more robust to the systemic biases that impact population-based methods.

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality.

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS.

The urban physical environment and leisure-time physical activity in early midlife: a FinnTwin12 study.

Under the exposome framework, this study examined the relationship between the urban physical environment and leisure-time physical activity during early midlife based on 394 participants (mean age: 37, range 34-40) from the FinnTwin12 cohort, residing in five major Finnish cities in 2020. We curated 145 urban physical exposures based on residential addresses and measured three outcomes: total leisure-time physical activity (total LTPA) and two sub-domains: leisure-time physical activity without commuting activity (LTPA) and commuting activity. K-prototypes clustering identified three urban clusters: "original city center," "new city center," and "suburban," each with distinct environmental patterns.

Genome-wide association studies of binge eating behaviour and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes.

Eating disorders -including anorexia nervosa (AN), bulimia nervosa, and binge eating disorder-are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. We conducted the first genomic meta-analysis of binge eating behaviour (BE; 39,279 cases, 1,227,436 controls), alongside new analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries).

Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region.

Cross-sectional study of plasma phosphorylated tau 217 in persons without dementia.

Introduction: Little is known about plasma phosphorylated tau 217 (p-tau217) in individuals without a clinical diagnosis of Alzheimer's disease (AD). We studied associations of plasma p-tau217 with age, sex, education, and genetic risk; estimated the heritability; and conducted a genome-wide association study (GWAS).

Methods: A population-based biobank recall study of 65- to 85-year-old twins ( = 697, mean [SD] age 76.

Proteomic associations with fluctuation and long-term changes in BMI: A 40-year follow-up study.

Introduction: While some studies have explored associations between weight change and blood proteins, most have been intervention-based, offering limited insight into proteomic associations with long-term weight gain. It remains unclear whether plasma proteins are related to BMI fluctuation over time. This study investigates associations of long-term BMI changes and fluctuations with over 1000 plasma proteins involved in cardiometabolic and inflammation functions.

Genetic Liability to Higher Muscle Strength Associates With a Lower Risk of Cardiovascular Disease Mortality in Men Irrespective of Leisure-Time Physical Activity in Adulthood: A Longitudinal Cohort Study.

Background: Low muscle strength predicts premature mortality. We determined whether genetic liability to muscle strength is associated with mortality and whether this association is influenced by long-term leisure-time physical activity (LTPA).

Methods And Results: We estimated the effects of a polygenic score for handgrip strength (PGS HGS) on all-cause and cardiovascular disease (CVD) mortality risk in the older Finnish Twin Cohort (N=8815, 53% women).

Genetic liability to sedentary behaviour and cardiovascular disease incidence in the FinnGen and HUNT cohorts.

Objective: Energy-saving sedentary behaviour may be an evolutionarily selected trait that is no longer advantageous. We investigated the associations between genetic liability to sedentary behaviour and the incidence of the most common cardiovascular disease (CVD).

Methods: We constructed and validated a genome-wide polygenic score for leisure screen time (PGS LST) as a measure of genetic liability to sedentary behaviour.

Proteomic associations with fluctuation and long-term changes in BMI: A 40-year follow-up study.

Introduction: While some studies have explored associations between weight change and blood proteins, most have been intervention-based, offering limited insight into proteomic associations with long-term weight gain. It remains unclear whether plasma proteins are related to BMI fluctuation over time. This study investigates associations of long-term BMI changes and fluctuations with over 1,000 plasma proteins involved in cardiometabolic and inflammation functions.

Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.

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.

Alcohol use in Early Midlife: Findings from the Age 37 Follow-Up Assessment of the FinnTwin12 Cohort.

This paper provides an overview of the most recent assessment, collected in early midlife, of the FinnTwin12 cohort, a population-based study of Finnish twins born in 1983-1987. The twins were invited to complete an online survey assessing a range of variables, including physical and mental health, alcohol use and problems, other substance use, and early midlife environments (e.g.

Genetic Liability to Cardiovascular Disease, Physical Activity, and Mortality: Findings from the Finnish Twin Cohort.

Purpose: We investigated whether longitudinally assessed physical activity (PA) and adherence specifically to World Health Organization PA guidelines mitigate or moderate mortality risk regardless of genetic liability to cardiovascular disease (CVD). We also estimated the causality of the PA-mortality association.

Methods: The study used the older Finnish Twin Cohort with 4897 participants aged 33 to 60 yr (54.

Genome-Wide Polygenic Score for Muscle Strength Predicts Risk for Common Diseases and Lifespan: A Prospective Cohort Study.

Background: We used a polygenic score for hand grip strength (PGS HGS) to investigate whether genetic predisposition for higher muscle strength predicts age-related noncommunicable diseases, survival from acute adverse health events, and mortality.

Methods: This study consisted of 342 443 Finnish biobank participants from FinnGen Data Freeze 10 (53% women) aged 40-108 with combined genotype and health registry data. Associations between PGS HGS and a total of 27 clinical endpoints were explored with linear or Cox regression models.