Evidence for Genetic Nurture Effects on Substance Use.

Substance use runs in families. Beyond genetic transmission, parental genetics can indirectly influence offspring substance use through the rearing environment, known as "genetic nurture". This study utilized transmitted and non-transmitted polygenic scores to investigate genetic nurture effects on tobacco, alcohol and cannabis use in up to 15,863 adults with at least one genotyped parent from the Lifelines cohort.

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.

Prospective associations between major depressive disorder, generalized anxiety disorder, fibromyalgia, and myalgic encephalomyelitis/chronic fatigue syndrome.

Background: Functional disorders (FDs) are associated with internalizing disorders (IDs). Studies investigating the nature of these associations over time are limited. We tested the direction of causation between measures of IDs (major depressive disorder [MDD], generalized anxiety disorder [GAD]) and FDs (fibromyalgia [FM] and myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS]) measured across two waves of longitudinal data ( = 108,034 and = 73,590).

Measuring the Associations Between Brain Morphometry and Polygenic Risk Scores for Substance use Disorders in Drug-Naive Adolescents.

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.

Practice effects persist over two decades of cognitive testing: Implications for longitudinal research.

Background: Repeated cognitive testing can boost scores due to practice effects (PEs), yet it remains unclear whether PEs persist across multiple follow-ups and long durations. We examined PEs across multiple assessments from midlife to old age in a nonclinical sample.

Method: Men (N=1,608) in the Vietnam Era Twin Study of Aging (VETSA) underwent neuropsychological assessment comprising 30 measures across 4 waves (~6-year testing intervals) spanning up to 20 years.

Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins.

The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.

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.

Clinical heterogeneity in major depressive disorder underlies comorbidity with functional disorders.

The comorbidities between MDD and functional disorders (FDs), such as fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS) remain largely unexplored. We analyzed data from 10,563 lifetime MDD cases (mean age = 50.5 (SD = 11.

The impact of genes and environment assessed longitudinally on psychological and somatic distress in twins from ages 15 to 35 years.

Background: Genetically informative twin studies have consistently found that individual differences in anxiety and depression symptoms are stable and primarily attributable to time-invariant genetic influences, with non-shared environmental influences accounting for transient effects.

Methods: We explored the etiology of psychological and somatic distress in 2279 Australian twins assessed up to six times between ages 12-35. We evaluated autoregressive, latent growth, dual-change, common, and independent pathway models to identify which, if any, best describes the observed longitudinal covariance and accounts for genetic and environmental influences over time.

Triangulated evidence provides no support for bidirectional causal pathways between diet/physical activity and depression/anxiety.

Background: Previous studies (various designs) present contradicting insights on the potential causal effects of diet/physical activity on depression/anxiety (and vice versa). To clarify this, we employed a triangulation framework including three methods with unique strengths/limitations/potential biases to examine possible bidirectional causal effects of diet/physical activity on depression/anxiety.

Methods: Study 1: 3-wave longitudinal study ( = 9,276 Dutch University students).

The Mechanisms Underlying the Intergenerational Transmission of Substance Use and Misuse: An Integrated Research Approach.

Substance 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.

Polygenic risk scores and help-seeking behaviour in young people with recent onset of mood and psychotic disorders.

Objectives: We examined associations between polygenic risk scores (PRS) for depression (PRS-MDD), psychosis (PRS-SCZ), bipolar disorders (PRS-BD) and neuroticism (PRS-NEU) and (i) help-seeking, and (ii) new onset cases of full-threshold mood or psychotic disorders in youth.

Methods: Help-seeking for mental health problems was assessed by self-report and mood and psychotic disorders were identified using the Composite International Diagnostic Interview. A principal component analysis of the four selected PRS identified two dimensions (BD-SCZ; MDD-NEU) that accounted for 69.

The genetic and environmental etiology of novel frequency-driven regional parcellations of abnormal white matter.

The prevalence of white matter disease increases with age and is associated with cerebrovascular disease, cognitive decline, and risk for dementia. MRI measures of abnormal signal in the white matter (AWM) provide estimates of damage, however, regional patterns of AWM may be differentially influenced by genetic or environmental factors. With our data-driven regional parcellation approach, we created a probability distribution atlas using Vietnam Era Twin Study of Aging (VETSA) data (n = 475, mean age 67.

A twin analysis to estimate genetic and environmental factors contributing to variation in weighted gene co-expression network module eigengenes.

Multivariate network-based analytic methods such as weighted gene co-expression network analysis are frequently applied to human and animal gene-expression data to estimate the first principal component of a module, or module eigengene (ME). MEs are interpreted as multivariate summaries of correlated gene-expression patterns and network connectivity across genes within a module. As such, they have the potential to elucidate the mechanisms by which molecular genomic variation contributes to individual differences in complex traits.

Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.

Introduction: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers.

Methods: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.

Comorbidity and sex differences in functional disorders and internalizing disorders.

Objective: In the current exploratory study we estimate comorbidity rates between FDs [fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS)]-and IDs-[major depressive disorder (MDD) and generalized anxiety disorder (GAD)] by using self-reported diagnostic criteria.

Method: We analyzed data from 107,849 participants (mean age = 49.3 (SD = 13.

Associations of plasma neurofilament light chain with cognition and neuroimaging measures in community-dwelling early old age men.

Background: Plasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations.

Methods: We examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.

Midlife cumulative deficit frailty predicts Alzheimer's disease-related plasma biomarkers in older adults.

Background: The study explores whether frailty at midlife predicts mortality and levels of biomarkers associated with Alzheimer's disease and related dementias (ADRD) and neurodegeneration by early old age. We also examine the heritability of frailty across this age period.

Methods: Participants were 1,286 community-dwelling men from the Vietnam Era Twin Study of Aging at average ages 56, 62 and 68, all without ADRD at baseline.

A Developmentally-Informative Genome-wide Association Study of Alcohol Use Frequency.

Contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. We applied genomic structural equation modeling to combine developmentally-informative phenotype data and GWAS to create polygenic scores (PGS) for alcohol use frequency that are specific to developmental stage. Longitudinal cohort studies targeted for gene-identification analyses include the Collaborative Study on the Genetics of Alcoholism (adolescence n = 1,118, early adulthood n = 2,762, adulthood n = 5,255), the National Longitudinal Study of Adolescent to Adult Health (adolescence n = 3,089, early adulthood n = 3,993, adulthood n = 5,149), and the Avon Longitudinal Study of Parents and Children (ALSPAC; adolescence n = 5,382, early adulthood n = 3,613).

Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals.

Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses.

Polygenic risk scores and the prediction of onset of mood and psychotic disorders in adolescents and young adults.

Aim: To examine whether polygenic risk scores (PRS) for neuroticism, depression, bipolar disorder and schizophrenia are higher in individuals manifesting trans-diagnostic risk factors for the development of major mental disorders and whether PRS enhance prediction of early onset full-threshold disorders.

Methods: Using data from the Brisbane Longitudinal Twin Study, we examined individual PRS for neuroticism, depression, bipolar disorder and schizophrenia, recorded evidence of subthreshold syndromes and family history of mood and/or psychotic disorders and noted progression to trans-diagnostic clinical caseness (onset of major mental disorders) at follow-up. We undertook multivariate, receiver operating curve and logistic regression analyses that were adjusted for known variables of influence (age, twin status, and so on).

The heritability of blood-based biomarkers related to risk of Alzheimer's disease in a population-based sample of early old-age men.

Introduction: Despite their increased application, the heritability of Alzheimer's disease (AD)-related blood-based biomarkers remains unexplored.

Methods: Plasma amyloid beta 40 (Aβ40), Aβ42, the Aβ42/40 ratio, total tau (t-tau), and neurofilament light (NfL) data came from 1035 men 60 to 73 years of age (μ = 67.0, SD = 2.

Higher cortical thickness/volume in Alzheimer's-related regions: protective factor or risk factor?

Some evidence suggests a biphasic pattern of changes in cortical thickness wherein higher, rather than lower, thickness is associated with very early Alzheimer's disease (AD) pathology. We examined whether integrating information from AD brain signatures based on mean diffusivity (MD) can aid in the interpretation of cortical thickness/volume as a risk factor for future AD-related changes. Participants were 572 men in the Vietnam Era Twin Study of Aging who were cognitively unimpaired at baseline (mean age = 56 years; range = 51-60).