Biomedical subjects

Renato Polimanti

Publications and source records attributed to Renato Polimanti.

5 recordsLinked to original sources

PubMed2026

Robust inference and correlates from genetic associations with personality.

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustness, their generalizability and the biological and social pathways through which they act. Here we meta-analyse data across 46 cohorts comprising 611,037 to 1.14 million 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 up to 50,725 participants for within-family GWAS. We identify 1,260 lead genetic variants associated with personality, including 824 novel variants3. Common genetic variants explain a moderate 4.8-9.3% of the variance in measures of each trait, and 9.3-13.3% among instruments with typical measurement reliability. Genetic associations with personality are highly consistent but not identical across geography, reporter (self versus close other), age group and measurement instrument, and we find minimal spousal assortment for personality in recent history. In contrast to many other social and behavioural traits4,5, within-family GWAS and polygenic index analyses indicate that genetic associations with personality are minimally confounded by the shared family environment. Polygenic prediction, genetic correlation and Mendelian randomization analyses indicate that personality traits have widespread, potentially causal associations with consequential behaviours and life outcomes. Overall, we find that the genetic architecture of personality is robustly generalizable, minimally confounded and widely relevant to human experience.

Journal Article↗

PubMed2026

Shared genetic architecture and neurobiological pathways of problematic alcohol use and anxiety disorders.

Problematic alcohol use (PAU) and anxiety disorders (ANX) frequently co-occur, implying shared genetic and neurobiological foundations. However, the directionality of potential causal relationships and the specific mechanisms underlying the overlap remain unclear. Thus, we investigated the shared genetic architecture and neurobiological pathways between PAU and ANX using a multimethod genomic approach. We analyzed summary statistics from genome-wide association studies (GWAS) of PAU and ANX using Mendelian Randomization to assess causal associations between ANX and PAU. We used MiXeR to assess the overall shared genomic architecture, Local Analysis of (co)Variant Association to estimate regional genetic correlations, and conjunctional false discovery rate (conjFDR) to identify individual overlapping loci. We used FUMA to map single-nucleotide polymorphisms (SNPs) to independent loci, conduct differential gene expression analyses across 30 general and 54 specific tissue types, and perform cell-type specificity analyses using a human brain cell atlas. Druggability of identified targets was also evaluated. Mendelian Randomization analyses indicated bidirectional causal associations between ANX and PAU. MiXeR identified moderate polygenic overlap (52.5%) and genetic correlation (rg = 0.44) between the traits, with high effect direction concordance among shared estimated causal variants (86.4%). ConjFDR identified 97 shared lead SNPs, of which 89 had concordant and 8 discordant effects on PAU and ANX. These loci mapped to 97 genes, including DRD2 and PDE4B, genes linked to dopaminergic and cAMP signaling pathways, respectively. Concordant gene expression was enriched in brain, nerve, adrenal gland, esophagus, stomach, and colon, with enriched expression specifically in the prefrontal cortex, anterior cingulate cortex, hippocampus, hypothalamus, substantia nigra and amygdala. FUMA cell-type enrichment analysis identified associations predominantly in neurons from the cerebral cortex, hippocampus, and thalamus. We found substantial genetic and neurobiological overlap between PAU and ANX, highlighting reciprocal, causal relationships between the traits, with differentially expressed genes enriched in addiction- and anxiety-relevant brain regions. These findings support shared genetic and neurobiological mechanisms linking PAU and ANX, while acknowledging that some signals may reflect broader internalizing or psychiatric liability.

Journal Article↗

PubMed2026

Assessing the comorbidity between asthma and depression through polygenic risk scoring and time-to-event models.

BACKGROUND: Patients with asthma have an increased risk of developing depression, affecting their quality of life. To date, the processes contributing to this comorbidity remain unclear. METHODS: We integrated two large genome-wide association studies (88,486 patients with asthma and 447,859 controls; 412,024 patients with depression and 1,587,577 controls) with cross-sectional and longitudinal information available from the All of Us Research Program (N = 87,167) through polygenic risk scoring (PRS), Cox proportional-hazards models, one-sample Mendelian randomization (MR), and gene-set and drug-repurposing analyses. RESULTS: We observed that depression PRS was associated with increased asthma risk (hazard ratio, HR = 1.13, 95% CI = 1.09-1.17), also when accounting for comorbidity status (HR = 1.08, 95% CI = 1.04-1.12). Conversely, the effect of asthma PRS was null after accounting for comorbidity status. One-sample MR analysis showed an effect of depression genetic liability on asthma, ranging from beta = 0.36 ± 0.03 when considering a linear relationship to beta = 3.21 ± 0.31 when considering possible nonlinear relationships. Conversely, the effect of asthma genetic risk on depression was null after accounting for potential confounders. The gene-set analyses showed that asthma and depression polygenic risks share biological processes, molecular functions, and cellular components related to the immune system and the lung-brain axis. CONCLUSIONS: Genetic predisposition contributes to asthma-depression comorbidity through direct effects and shared pathogenic processes. These findings highlight the potential to develop targeted interventions to prevent and treat the co-occurrence of respiratory and neuropsychiatric disorders.

Comorbidity↗

PubMed2025

Developmental timing of index trauma exposure and accelerated epigenetic aging in United States military veterans.

Trauma exposure has been linked to accelerated GrimAge, an epigenetic biomarker of premature morbidity and mortality. Building on this evidence, the present study examined whether the type and timing of index trauma exposure are differentially associated with accelerated GrimAge. Participants were 873 European American male United States military Veterans from the National Health and Resilience in Veterans Study. We investigated associations between self-reported age at index trauma, index trauma type (interpersonal violence, non-interpersonal trauma, or loss/instability/other), and accelerated GrimAge, operationalized as GrimAge exceeding chronological age by five or more years. Results revealed that interpersonal violence was associated with three-fold greater odds of accelerated GrimAge compared to other trauma types. Age at index trauma was not independently associated with accelerated GrimAge. However, we observed a significant interaction between trauma type and its developmental timing, even after adjusting for index trauma recency, cumulative trauma burden, and other potential confounders. Specifically, Veterans who were older at the time of exposure to interpersonal violence or trauma involving loss or instability had higher odds of accelerated GrimAge. In contrast, exposure to non-interpersonal trauma was more strongly associated with accelerated GrimAge when it occurred at younger ages. These results indicate that trauma type and timing jointly influence epigenetic aging in Veterans, highlighting the need for tailored interventions that address specific trauma characteristics to reduce associated long-term health risks in this population.

Humans↗

PubMed2025

The landscape of suicide risk factors in Latin America.

Suicide is a leading cause of death globally, with over 75 % of cases occurring in low- and middle-income countries (LMICs). Latin America, a severely underrepresented region in suicide research, has experienced a 6 % increase in its suicide rate from 2010 to 2016, contrasting with a global decline. In this commentary, we provide an overview of the epidemiological, social, and clinical factors influencing suicide in Latin America. We highlight the distinct trends in Latin America compared to other world regions, including the significant disparities in mental health care accessibility. Our review also considers the role of sociocultural factors such as strong family ties, traditional gender norms, and the impact of religiosity on stigma and care-seeking behaviors. Additionally, we address the lack of representation of Latin American populations in genetic studies on suicide, which hinders the identification of relevant biological markers and the development of tailored interventions. We call for increased research on the clinical, genetic, and social determinants of suicide in this region to better understand risk factors and ultimately inform suicide prevention strategies. Addressing this gap is critical for reducing suicide rates in Latin America.

Humans↗