Processing speed (PS), the rate at which an individual can perform basic cognitive tasks, and executive functions (EFs), cognitive abilities regulating thoughts and action, are key cognitive abilities related to important life outcomes. We investigated the relationship between PS and multiple EFs (a common factor and two factors specific to updating working memory and shifting mental sets) across adolescence (M age = 17.26 years, SD = 0.68) and established adulthood (M age 29.34 years, SD = 1.29). 797 individual twins (MZ = 428, DZ = 369) in the Colorado Longitudinal Twin Study completed 3 PS tasks and 6–9 EF tasks. PSage16 correlated strongly with PSage29 (r = .90) and Common EF (cEF) at age 17 (r = .70). Furthermore, cEF and Updating-Specific factors in late adolescence predicted new variance in PSage29 (rs = 0.13 to 0.16), but PSage16 did not predict new variance in cEF in established adulthood. PS and cEF were highly heritable at both ages (a2 > = 0.74) and genetically correlated at both time points (ra = 0.70 to 0.73). PS was not significantly genetically correlated with the Updating- or Shifting-Specific factors in late adolescence, but was in established adulthood. Results indicate that PS and EFs are highly correlated yet distinct constructs. PS and EFs both demonstrate strong stability of genetic/environmental influences across nearly 15 years from late adolescence into established adulthood. It will be important for future developmental studies to understand why specific EF factors predict future variance in PS, but not the reverse.

Evidence that inflammation is related to poorer mental health largely comes from clinical samples. This pre-registered study examined whether these findings extend to depression, alcohol use, and alcohol use disorder (AUD) in a large sample of community adults (N=972, M=33.4 years, range=28-49), including a subset of participants from same-sex twin pairs. Analyses primarily examined C-reactive protein (CRP) and a pro-inflammatory cytokine index of three cytokines: interleukin(IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-⍺). This pro-inflammatory index averaged the three cytokines after each was placed on a standard-normal distribution (M=0[SD=1]). Covariates were age, sex, diet relevant measures, and anti-depressant use. Further, we pre-registered analyses to follow up significant effects in the full sample with co-twin control analyses, which compare twins to each other to control confounds that make twins similar. Depression, alcohol use, and AUD were unrelated to CRP and the pro-inflammatory index. Notably, AUD was associated with lower levels of four individual cytokines (after multiple-testing correction): IL-1β, IL-4, IL-10, and IL-12. In co-twin control analyses, however, these negative associations were nonsignificant, suggesting familial confounders explain these associations. These findings suggest that associations between cytokines and indices of depression and alcohol behavior may not extend from clinical to community samples. Further, although this study is the first that applies the co-twin control approach to rigorously test the link between inflammation and alcohol behavior, it largely converges with studies that suggest confounders explain the putative protective effect of alcohol behaviors on inflammatory markers of health.

OBJECTIVES:Early-life rural-urban residence has been linked to differences in later-life cognitive functioning and dementia risk. However, the contextual pathways underlying these associations, particularly emergent associations later in life, remain underexplored. We examined the associations between young adult urbanicity and domain-specific cognition in older adulthood and whether late midlife neighborhood socioeconomic disadvantage may mediate such associations. METHODS:Participants were 881 community-dwelling men aged 61-73 from across the United States. Young adult urbanicity (rural, suburban, and urban) was assessed at a mean age of 20 based on the Rural-Urban Continuum Codes. Late midlife neighborhood disadvantage was indexed by the area deprivation index (ADI), and cognitive performance in older adulthood was assessed in five domains: executive function, episodic memory, processing speed, verbal fluency, and visual-spatial ability. RESULTS:Compared to those in rural areas, participants who resided in urban areas during young adulthood had lower late midlife ADI (β = -0.85, p < .05), and better executive function (β = 0.19), processing speed (β = 0.24), and verbal fluency (β = 0.30) (ps < .05) in older adulthood. ADI partially mediated these associations, such that urban residence was associated with lower ADI, which was then associated with better performance in these three domains (indirect effects: βs = 0.02 to 0.03). DISCUSSION:Late midlife neighborhood disadvantage represents a contextual pathway linking early-life rural-urban residence to cognitive function in older adulthood. Reducing socioeconomic disadvantage through health policies and interventions at both the community-level early in life and the neighborhood-level later in life may help reduce the risk of cognitive impairment and dementia.

Prosody perception is an often overlooked aspect of human language despite its importance in facilitating spoken language comprehension. Sensitivity to prosodic cues varies between individuals, and prosody perception skills are shown to be associated with various language- and reading-related outcomes. Despite the importance of prosody perception in human communication, its underlying biology is poorly understood. This study investigates the genetic architecture of prosody (speech rhythm) perception and explores its evolutionary roots. We conducted a GWAS of prosody (n = 1,501) as measured by scores on the Test of Prosody via Syllable Emphasis ("TOPsy"). GWAS results yielded 14 suggestive significant signals (p < 5.00 × 10-6). Gene set enrichment analysis identified shared genetic architecture between human prosody perception and key vocal learning brain regions in songbirds, suggesting that human prosody perception may have evolutionary convergence in communication mechanisms in animal vocal learning. Additionally, cross-trait polygenic score analyses suggest shared genetic influences between prosody perception and both word reading and musical beat synchronization, emphasizing how genetics influence prosody perception and its associations with communication-, education-, and music-related traits. These initial efforts could inform advances in communication sciences and disorders as well as educational contexts.

Background:As sleep data from wearable devices are increasingly available in health research, there are new opportunities to understand sleep regulation behaviors as modifiable risk factors for disease. At such a large scale (tens of thousands of people over millions of day-level observations), prioritizing and interpreting sleep behaviors is challenging while maintaining biological relevance and modifiability. In this work, we aim to address this challenge by proposing a framework to interpret Fitbit data through a well-known neurobiological framing of sleep regulation, the two-process model. Methods:We use data from the All of Us Research Program, a national biobank with passively collected Fitbit data for 32,292 people across 15,754,893 total days. We map Fitbit behaviors (b) to either circadian (C) or homeostatic (S) processes. Using iterative exploratory factor analysis to obtain weights, the Fitbit Cb and Sb are then weighted at the level of each day to create Cb and Sb scores. Findings:Cb and Sb scores were found to align with expected real-world relationships with age, seasonality, shift work, and napping. Cb and Sb scores were interpreted with relation to depression, where it was found that Sb scores are highly associated with likelihood of diagnosis (OR = 1.5, p < 2e-16) while Cb and Sb scores are equally associated with severity (Sb score β = 0.2, Cb score β = 0.21, p < 2e-16). Interpretation:Cb and Sb scores support longitudinal interpretation (e.g., changes in Sb around treatment), aggregation (e.g., differences in Cb between two groups), and actionable modification (e.g., reduce naps to improve poor Sb). Overall, our behavior scores allow for interpretation of wearables sleep data and can be utilized across many disease contexts to better understand how sleep influences health.

OBJECTIVE:Adolescence is a critical developmental window for shaping substance use trajectories. Music engagement during this period may reduce substance experimentation and later misuse through direct effects or shared etiological influences, and these associations may differ by genetic risk. METHOD:Using a genetically informed, longitudinal design, we analyzed associations between music engagement at Age 12 and substance use outcomes at Ages 17 and 23 in the Colorado Longitudinal Twin sample (413 same-sex twin pairs; 50% female; 91.9% White; 9.1% Hispanic). Music engagement and substance use were assessed using questionnaires developed for this study. Twin modeling was used to disentangle causal from etiological influences, and polygenic scores were used to test whether associations are strongest for those at highest genetic risk. RESULTS:Music engagement was associated with less alcohol use and substance experimentation across adolescence and young adulthood (r = -0.105 to -0.099, p < .05). These associations were primarily attributable to shared environmental factors (rC = -0.56 to -0.41, p < .05), with some genetic overlap estimated in the opposite direction (rA = 0.55-0.61, p < .05). Sensation seeking polygenic scores predicted music engagement (b = 0.123, p = .006), but gene-environment interactions were nonsignificant. CONCLUSIONS:Music engagement is associated with reduced substance use in adolescence and young adulthood, driven by protective shared environmental influences rather than direct effects. Music engagement may represent a constructive environmental outlet for youth, underscoring the importance of genetically informed research. However, the results may not generalize to more contemporary and/or diverse cohorts. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Background and Objectives:Cognitive dispersion, reflecting intraindividual variability across tasks, may signal dementia risk in older adults, but its origins and relevance before midlife are unclear. We examined dispersion as a potential marker of cognitive reserve in established adulthood and distinguished it from general ability using heritability analyses. Research Design and Methods:1,245 primarily non-Hispanic White twins and siblings were assessed at 33.3 years (SD = 5.0; 53% female) using 2 cognitive batteries. Bayesian mixed effects location scale models estimated mean performance and dispersion across cognitive tasks, with tasks standardized against current sample-based norms (age 33) and adolescent norms (age 16). The mean of task scores standardized to current norms reflects current ability, while the mean of the same scores standardized to adolescent norms reflects growth in ability. The respective dispersion estimates represent task-specific deviations from general ability and task-specific gains. Results:Across 4 models fitted by battery and standardization, greater cognitive dispersion was associated with higher general ability (r = 0.23-0.56) and developmental gains (r = 0.62-0.93). Verbal tasks showed lower dispersion relative to performance tasks (β = 0.83-0.87). Dispersion was strongly heritable overall (43%-84%), and moderately heritable independent of general ability (36%-37%) and growth (2%-16%). Dispersion did not predict education or occupational outcomes beyond general ability and growth. Discussion and Implications:Before midlife, cognitive dispersion is distinct from general ability and moderately heritable. Dispersion is associated with higher cognitive ability and growth, but not directly with educational or occupational attainment, suggesting dispersion may relate to cognitive reserve through other pathways.

Childhood maltreatment has been implicated in adulthood externalizing behaviors. However, this relationship could be explained by confounding factors (e.g., externalizing risk factors that co-occur with childhood maltreatment), rather than a direct effect of maltreatment on externalizing behavior. The current study extends this research using a longitudinal sibling study. Specifically, we leveraged the sibling-comparison design, which compares siblings from the same family to each other to examine whether greater maltreatment exposure at baseline (M age = 16.9) is associated with greater increases in externalizing behavior through young adulthood (M age = 29.1). Thus, this approach controls for familial risk factors shared by siblings. Participants included 365 probands and 376 siblings who were followed across three assessment waves. Participants were administered clinical interviews at each wave to assess alcohol use disorder (AUD), illicit substance use disorder (SUD), and antisocial behavior (ASB), and a self-report survey of exposure to physical abuse, emotional abuse, sexual abuse, and neglect. Greater adolescent exposure to neglect and physical abuse were both associated with greater adolescent levels of AUD and ASB. Adolescent physical abuse, but not neglect, was also associated with greater illicit SUD symptoms. Additionally, greater emotional abuse was associated with steeper increases in AUD and illicit SUD symptoms through young adulthood. Importantly, none of these effects were explained by familial confounds. These findings provide strong evidence for adolescent emotional abuse playing a causal role in later AUD/SUD, suggesting that preventing such abuse and mitigating its effects may have downstream effects on reducing AUD/SUD.

Active music engagement, that is, playing a musical instrument or singing, may be protective of motor function decline in aging. Although playing a musical instrument may transfer to benefits in motor function, it is also possible that the genetic architecture of motor behavior and the motor system brain structures may influence active music engagement. This study investigated whether polygenic scores (PGSs) for five behavioral motor traits, 12 structural brain traits, and seven rate-of-change in brain structure traits trained from existing genome-wide association studies predict active music engagement in four independent cohorts: the Canadian Longitudinal Study on Aging (CLSA; N = 22,198), Wisconsin Longitudinal Study (WLS; N = 4605), Vanderbilt's BioVU Repository (BioVU; N = 6150), and Vanderbilt's Online Musicality Study (OM; N = 1559). Results were meta-analyzed for each PGS main effect across outcomes and cohorts, revealing that PGS for a faster walking pace was associated with higher amounts of active music engagement. Within CLSA, a higher PGS for walking pace was associated with greater odds of engaging with music. Our findings suggest a shared genetic architecture between motor function and active music engagement. Future research should consider the genetic underpinnings of motor behavior when evaluating the effects of music engagement on motor function.

BACKGROUND AND AIMS:Addiction-related behaviors, such as loss of control eating (LOC), cigarette smoking and alcohol consumption, have been associated with high body mass index (BMI). This study aimed to assess genetic and environmental contributions to these associations over time. DESIGN:A longitudinal twin study using data from waves 2 and 3 of the Center on Antisocial Drug Dependence study, employing additive genetic (A), shared environmental (C), nonshared environmental (E) influences and cross-lagged models. SETTING:Colorado, USA. PARTICIPANTS:The sample included 764 male and 997 female same-sex twins. MEASUREMENTS:BMI was calculated using self-reported height and weight. LOC was self-reported. Cigarettes smoked per day (CPD) and drinks per week (DPW) were assessed during interviews. FINDINGS:We conducted three cross-lagged models: LOC and BMI in males, LOC and BMI in females and CPD and BMI in females, after excluding small phenotypic correlations (|r| < 0.10). Trait stability over time was largely attributable to genetic factors, accounting for 62% of the variance in BMI (both sexes), 11% in LOC (males), 18% in LOC (females) and 56% in CPD (females) at wave 3. Residual effects were mostly from nonshared environmental factors, accounting for 38% of the variance in BMI (both sexes), 76% of LOC (females), 71% of LOC (males) and 44% of CPD (females) at wave 3. A small but statistically significant cross-lagged effect occurred from wave 2 BMI to wave 3 LOC, explaining 12% (males) and 3% (females) of the variance in wave 3 LOC, with genetic factors accounting for most of this effect. No cross-lagged effects emerged from LOC or CPD to BMI. CONCLUSIONS:Genetic factors contributing to higher body mass index at an earlier age may also increase the risk of developing loss of control eating later in life, highlighting the importance of early weight-related interventions to prevent the onset of disordered eating behaviors.

Adolescent pain complaints may be related to genetic risk for chronic pain across the life course. Identifying whether adolescent pain is genetically linked to chronic pain in adulthood can advance understanding of pain etiology and inform early intervention. Two waves of pain assessments were used from the Adolescent Brain Cognitive Development (ABCD) study, a population-based sample of 11,876 adolescents. The analyses included 6,387 adolescents of European-like ancestry (mean ages = 12.03 and 12.93 at waves 2 and 3; 52% males), with 94.0% retention across waves. Two polygenic scores (PGSs) were constructed using genome-wide association study summary statistics from up to 435,917 adults in the UK Biobank. One PGS captured shared genetic risk across 24 pain conditions (General Chronic Pain), while the second captured additional musculoskeletal-specific genetic risk across 11 conditions after adjusting for general pain (Musculoskeletal-specific Pain). Mixed-effects models were used to examine associations between these PGSs and adolescent self-reported pain presence, intensity, recurrence, and multi-site pain. Across both waves, 36.0%-37.0% adolescents reported pain. The General Pain PGS was associated with pain presence (b=0.07, OR=1.07, 95%CI=1.02-1.13, FDR-corrected p=0.023) and intensity (b=0.14, 95%CI=0.07-0.21, FDR-corrected p<0.001); but not recurrent pain (b=0.08, OR=1.08, 95%CI=1.01-1.16, FDR-corrected p=0.091) or multi-site pain (b=0.01, OR=1.00, 95%CI=0.94-1.07, FDR-corrected p=0.958). The Musculoskeletal-specific Pain PGS was not significantly associated with the outcomes. Genetic risk for chronic pain in adulthood, as measured by PGSs, is associated with adolescent pain complaints. Adolescent pain signals early vulnerability for chronic pain, highlighting adolescence for early intervention. Perspective This study links adolescent pain to polygenic risk for adult chronic pain, suggesting that early pain reflects enduring genetic liability and reflects central pain processes. These results provide mechanistic insight into chronic pain across the lifespan and highlight adolescence as a period for intervention.

Music engagement traits are linked to important developmental language, cognitive, and mental health outcomes, but longitudinal studies have not examined the developmental stability of music engagement across the first few decades of life, especially using genetically informative designs. The current study examined music engagement—defined as being interested and skilled at musical instruments and taking music lessons—across four timepoints in childhood and adolescence to test the hypothesis that genetic influences explain an increasingly larger proportion of variance over time. We also examined how these measures relate to the frequency of music engagement and music listening in adulthood. Analyses were based on archival data from 1878 individuals in the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife), who completed self-reported measures of music engagement at ages 7, 10, 12, and 16 years, and two additional items in established adulthood (mean age 33 years). Results indicated that music engagement was moderately stable throughout childhood and adolescence ( r = 0.20 to 0.49). Heritability was larger in males than in females, but only in childhood, with greater stability of shared environmental influences in female children. These measures were modestly correlated with the frequency of musical instrument playing in adulthood ( r = 0.07 to 0.29) but not the frequency of music listening. These findings suggest that early music engagement is a dynamic phenotype that changes considerably between childhood, adolescence, and beyond. This work highlights the need for a developmental perspective in theoretical models of music engagement and its relation to language, cognition, and health.

BACKGROUND:There are well-known phenotypic and genetic associations among impulsivity, sensation seeking (SS), and alcohol consumption, but whether they vary between adolescence and early adulthood remains unclear. PURPOSE/HYPOTHESES:We hypothesized that adolescent alcohol consumption would be better predicted by polygenic indices (PGIs) of impulsivity and SS than PGIs of adult alcohol consumption (drinks per week; DPW), but that the reverse would be observed in young adulthood (i.e., stronger associations for DPW PGIs). METHODS:N = 733-754 twins of European genetic ancestry from the Colorado Longitudinal Twin Study were assessed at age 17 and/or 23 years using structural equation modeling. RESULTS:The SS PGIs were associated with alcohol consumption in adolescence (β=0.16), whereas DPW PGIs were associated with alcohol consumption in early adulthood (β=0.15). Additionally, phenotypic measures of impulsivity and SS are associated with alcohol consumption at both ages (β=.13-.21) and mediated some PGI-alcohol associations. DISCUSSION:These findings suggest that genetic influences on alcohol consumption change from adolescence to early adulthood, with genetic influences on sensation seeking most relevant to alcohol consumption in adolescence.

BACKGROUND: Psychiatric disorders affect approximately 20% of adolescents in the United States and are both heritable and highly polygenic. Polygenic scores (PGSs) aggregate genetic risk across the genome and in doing so potentially capture multiple, distinct behavioral pathways. Among these, cognitive control and reward sensitivity are key constructs that have been found to be independently and jointly related to adolescent psychopathology. METHODS: In this study, we used latent variables representing cognitive control and reward sensitivity (measured at baseline) as mediators between PGSs for internalizing, neurodevelopmental, and addiction-related psychopathology and observed psychopathology measured 2 years later in the ABCD (Adolescent Brain Cognitive Development) Study (N = 11,875; ages 9-12 years; 48% female, 52% male assigned at birth). RESULTS: Our findings show that most of the associations between PGSs and later psychopathology were accounted for by indirect effects through cognitive control and reward sensitivity; all of the associations between the addiction PGS and externalizing were accounted for by the indirect effects, but less of the internalizing PGS to internalizing pathway was accounted for by control and reward sensitivity. Multiple cognitive control factors significantly mediated the effects of PGSs on both internalizing and externalizing outcomes (indirect effects = 0.004-0.074). Reward sensitivity, specifically sensation seeking, uniquely mediated the association between the addiction PGS and later psychopathology, suggesting that addiction-related genetic risk may operate through pathways related to heightened reward responsiveness. CONCLUSIONS: Overall, these results indicate that PGSs for internalizing, neurodevelopmental, and addiction-related traits index multiple distinct behavioral mechanisms with specific relevance to adolescent psychopathology risk.

Concerns about memory often increase with age and have been suggested as a precursor to impending memory impairment or dementia. However, subjective memory concern (SMC) has also been shown to reflect an individual’s trait-like tendency to worry about memory, which is more strongly linked to negative affect than to objective memory performance. Despite behavioral evidence supporting a trait-like dimension of SMC, its neuroanatomical underpinnings remain underexplored. In 477 community-dwelling dementia-free men (56–72 years old), we investigated the association between SMC and cortical mean diffusivity (cMD)—a diffusion MRI-based metric of gray matter microstructural integrity—generating a brain-wide map of their association. Self-report trait anxiety and depressive symptoms were collected, along with objective memory scores based on three neuropsychological tasks for which brain maps of their association with cMD were also generated. Finally, we conducted spatial correlational analyses to compare the spatial patterns of these brain association maps to assess whether there were significant spatial resemblances between each. We found that the gray matter integrity correlates of SMC spatially resembled those of depressive symptoms and trait anxiety but not those of objective memory. The spatial correspondences between gray matter integrity correlates of negative affect measures and SMC were significantly stronger than those between SMC and objective memory. Together, these results suggest a neuroanatomical basis of trait-like SMC, which should be distinguished from state-related SMC that may be a precursor of objective memory deficits in research and clinical settings.

BACKGROUND:The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain. METHODS:Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI. RESULTS:Moderate-to-severe, but not mild, chronic pain intensity (β = -.10) and interference (β = -.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = -.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05). DISCUSSION:Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.

Measures of general cognitive ability (GCA) are highly stable from adolescence onward, particularly at the level of genetic influences. In contrast, measurement of GCA in early life (before 3 y old) is less reliable and less is known about the stability of GCA across this period, including its relation to adult GCA. Using data from the Colorado Longitudinal Twin study (N = 1,098), we examined the stability of GCA measures across 5 time-points (years 1 to 2, 3, 7, 16, and 29), including how an array of cognitive measures given at 7 and 9 mo relate to later GCA. We then examined the genetic and environmental stability of GCA across the first 30 y of life using complementary methods: twin analyses and polygenic scores (PGSs). Two infant cognition measures, object novelty and tester-rated task orientation, predicted GCA in adulthood (r = 0.16 and 0.18, respectively). Correlational analyses were consistent with a pattern of increasing stability across development for GCA measures between year 1 to 2 and adulthood (r = 0.39 to 0.85). Subsequent twin analyses revealed that 22% of variance in adulthood GCA was captured by genetic influences on GCA from year 3 or earlier, with an additional 10% explained by shared environmental influences on GCA at year 1 to 2. PGSs for adulthood GCA and educational attainment predicted GCA from 1 to 2 y onward (βs = 0.09 to 0.44) but not infant cognition. Findings suggest that genetic and environmental influences on GCA demonstrate considerable stability as early as age 3 y, but that measures of infant cognition are less predictive of later cognitive ability.

Delay discounting (DD), a person’s preference for smaller immediate rewards over larger delayed rewards, is a heritable trait that is associated with psychiatric and physical outcomes, yet the biological mechanisms underlying these links are not known. We performed a GWAS of DD using 134,935 23andMe research participants and identified 11 genome-wide significant loci. We did not replicate our previously reported association with rs6528024 (chrXq13.3, GPM6B; P = 5.30 × 10−02). The SNP-heritability of DD was 9.85 ± 0.57%. We observed genetic correlations between DD and 73 behavioral, physical, and neuroimaging traits, many of which persisted even after accounting for educational attainment, intelligence, and executive function. Network analysis revealed that the associations between DD and certain traits were explained by both overlapping and trait-specific biological processes. In a hospital-based cohort (N = 66,917), DD polygenic scores were associated with 212 medical conditions. These results demonstrate that DD has a pleiotropic and polygenic common variant architecture, and is genetically associated with numerous outcomes, making it a promising endophenotype for psychiatric and physical health.

BACKGROUND:Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear. METHODS:We used genomic structural equation modeling and genome-wide association studies (N = 79,729-903,147) to examine the latent genetic architecture of nine impulsivity traits and seven substance use (SU) and SUD traits. RESULTS:We found that the SU and SUD factors were strongly genetically inter-correlated (rG=0.77) but their associations with impulsivity facets differed. Lack of premeditation, negative and positive urgency were equally positively genetically correlated with both the SU (rG=.0.30-0.50) and SUD (rG=0.38-0.46) factors; sensation seeking was more strongly genetically correlated with the SU factor (rG=0.27 versus rG=0.10); delay discounting was more strongly genetically correlated with the SUD factor (rG=0.31 versus rG=0.21); and lack of perseverance was only weakly genetically correlated with the SU factor (rG=0.10). After controlling for the genetic correlation between SU/SUD, we found that lack of premeditation was independently genetically associated with both the SU (β=0.42) and SUD factors (β=0.21); sensation seeking and positive urgency were independently genetically associated with the SU factor (β=0.48, β=0.33, respectively); and negative urgency and delay discounting were independently genetically associated with the SUD factor (β=0.33, β=0.36, respectively). CONCLUSIONS:Our findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.

Phenotypic investigations have shown that actively engaging with music, i.e., playing a musical instrument or singing may be protective of motor decline in aging. For example, music training associated with enhanced sensorimotor skills accompanied by changes in brain structure and function. Although it is possible that the benefits of active music engagement "transfer" to benefits in the motor domain, it is also possible that the genetic architecture of motor behaviour and the motor system structure may influence active music engagement. This study investigated whether polygenic scores (PGS) for five behavioural motor traits, 12 neuromotor structural brain traits, and seven rates of change in brain structure traits trained from existing discovery genome-wide association studies (GWAS) predict active music engagement outcomes in four independent cohorts of unrelated individuals of European ancestry: the Canadian Longitudinal Study on Aging (CLSA; N=22,198), Wisconsin Longitudinal Study (WLS; N=4,605), Vanderbilt's BioVU Repository (BioVU; N=6,150), and Vanderbilt's Online Musicality study (OM; N=1,559). Results were meta-analyzed for each PGS main effect across outcomes and cohorts, revealing that PGS for a faster walking pace was associated with higher amounts of active music engagement. Within CLSA, a higher PGS for walking pace was associated with greater odds of engaging with music. Findings suggest a shared genetic architecture between motor function and active music engagement. Future intervention-based research should consider the genetic underpinnings of motor behavior when evaluating the effects of music engagement on motor function across the lifespan.