Renato Polimanti

Verified

Renato verified their affiliation via an institutional email.

Learn more

Verified

Renato verified their affiliation via an institutional email.

Learn more

• PhD
• Professor (Associate) at Yale University

INTRODUCTION Limited information is available regarding sex differences in the relationship of socioeconomic status and cognitive performance with Alzheimer's disease and related dementias (ADRD) family history. METHODS Leveraging the UK Biobank (N = 448,100) and All of Us Research Program (N = 240,319), we conducted observational and genetically...

This study explores the genetic link between gastrointestinal disorders and valvular heart disease (VHD), aiming to clarify shared mechanisms through a genome-wide pleiotropy analysis. We assessed the genetic correlation between six gastrointestinal disorders—including GERD, IBS, PUD, IBD, Crohn’s disease, and ulcerative colitis—and VHD, employing...

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 personal...

Gulf War Illness (GWI) is a multi-symptom chronic condition that affects Veterans who served in the 1990–1991 Gulf War (GW). To generate novel information about GWI pathogenesis, we used genome-wide data available from 33 523 Veterans of diverse ancestral backgrounds who served during the 1990–1991 Gulf War era (34% deployed). Polygenic score (PGS)...

Background To understand the pathogenetic mechanisms shared among schizophrenia (SCZ), bipolar disorder (BP), and major depression (MDD), we investigated the pleiotropic mechanisms using large-scale genome-wide and brain transcriptomic data. Methods We analyzed SCZ, BP, and MDD genome-wide association datasets available from the Psychiatric Genomi...

This study investigated the genetic and epigenetic mechanisms underlying the comorbidity of five substance dependence diagnoses (SDs; alcohol, AD; cannabis, CaD; cocaine, CoD; opioid, OD; tobacco, TD). A latent class analysis (LCA) was performed on 22,668 individuals from six cohorts to identify comorbid DSM-IV SD patterns. In subsets of this sampl...

Psychiatric disorders and symptoms are associated with differences in pain perception and sensitivity. These differences can have important implications in treating spinal degenerative disease (SDD) and chronic low-back pain (CLBP). Leveraging data from the UK Biobank (UKB) and the All of Us Research Program (AoU), we investigated the effects linki...

Background The development of posttraumatic stress disorder (PTSD) is attributable to the interplay between exposure to severe traumatic events, environmental factors, and biological characteristics. Blood and brain imaging markers have been associated with PTSD. However, to our knowledge, no study has systematically investigated the genetic relati...

To investigate the pleiotropic mechanisms linking brain structure and function to alcohol drinking and tobacco smoking, we integrated genome-wide data generated by the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN; up to 805,431 participants) with information related to 3935 brain imaging-derived phenotypes (IDPs) available from...

Importance Although psychological traumas have been associated with endometriosis, limited information is available regarding the role of trauma type and genetic predisposition. Objective To examine the relationship between traumatic experiences and endometriosis using observational and genetically informed analyses. Design, Setting, and Particip...

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 A...

In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichm...

Background Alcohol Use Disorder (AUD) affects over 15 million individuals in the United States, contributing to oxidative stress, neuroinflammation, and elevating the risk of neurodegeneration. Despite this, the connection between AUD and aging conditions, particularly Alzheimer’s disease (AD), remains unclear. AD, with a heritability of 60‐80%, is...

Background Alcohol use is hypothesized to be a risk factor for cognitive impairment (CI) and Alzheimer’s disease (AD). However, its role is often complex in diagnosing and distinguishing alcoholic dementia from AD. Hence, several AD‐focused studies exclude participants with possible alcohol misuse history, creating major challenges to investigate t...

Experiencing a traumatic event may lead to Posttraumatic Stress Disorder (PTSD), including symptoms such as flashbacks and hyperarousal. Individuals suffering from PTSD are at increased risk of cardiovascular disease (CVD), but it is unclear why. This study assesses shared genetic liability and potential causal pathways between PTSD and CVD. We lev...

Background Alcohol Use Disorder (AUD) affects over 15 million individuals in the United States, contributing to oxidative stress, neuroinflammation, and elevating the risk of neurodegeneration. Despite this, the connection between AUD and aging conditions, particularly Alzheimer’s disease (AD), remains unclear. AD, with a heritability of 60‐80%, is...

This study explores the genetic and epidemiologic correlates of long-term photoplethysmography-derived pulse rate variability (PRV) measurements with anxiety disorders. Individuals with whole-genome sequencing, Fitbit, and electronic health record data (N = 920; 61,333 data points) were selected from the All of Us Research Program. Anxiety polygeni...

International collaborations between high-income countries (HICs) and low- and middle-income countries (LMICs) have become increasingly essential in advancing global health, particularly within psychiatric research. These partnerships not only accelerate scientific discovery and enhance public health, but they also bring to light significant challe...

International collaborations between high-income countries (HICs) and low- and middle-income countries (LMICs) have become increasingly essential in advancing global health, particularly within psychiatric research. These partnerships not only accelerate scientific discovery and enhance public health, but they also bring to light significant challe...

This cross-sectional study uses data from 1135 male, European-American US military veterans to assess whether risk and protective factors influenced associations between posttraumatic stress disorder and epigenetic age.

Background Veterans of the 1990–1991 Gulf War have experienced excess health problems, most prominently the multisymptom condition Gulf War illness (GWI). The Department of Veterans Affairs (VA) Cooperative Studies Program #2006 “Genomics of Gulf War Illness in Veterans” project was established to address important questions concerning pathobiologi...

Objective: This study investigated the genetic and epigenetic mechanisms underlying the comorbidity patterns of five substance dependence diagnoses (SDs; alcohol, AD; cannabis, CaD; cocaine, CoD; opioid, OD; tobacco, TD). Methods: A latent class analysis (LCA) was performed on 31,197 individuals (average age 42+-11 years; 49% females) from six coho...

We leveraged information from more than 1.2 million participants, including 97,383 cases, to investigate the genetics of anxiety disorders across five continental groups. Through ancestry-specific and cross-ancestry genome-wide association studies, we identified 51 anxiety-associated loci, 39 of which were novel. In addition, polygenic risk scores...

Evening chronotypes (a.k.a. night-owls) are held to be at greater risk for psychiatric disorders. This is postulated to be due to delayed circadian timing increasing the likelihood of circadian misalignment in an early-oriented society. Circadian misalignment is known to heighten sleep inertia, the difficulty transitioning from sleep to wake charac...

There is a high prevalence of antisocial personality disorder (ASPD) in individuals affected by substance use disorders (SUD). However, there is limited information on the specific patterns of association of ASPD with SUD severity and specific SUD diagnostic criteria. We investigated the association of alcohol, cannabis, cocaine, opioid, and tobacc...

BACKGROUND Patients with post-traumatic stress disorder (PTSD) experience higher risk of adverse cardiovascular (CV) outcomes. This study explores shared loci, and genes between PTSD and CV conditions from three major domains: CV diagnoses from electronic health records (CV-EHR), cardiac and aortic imaging, and CV health behaviors defined in Life’s...

One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the...

INTRODUCTION While higher socioeconomic factors (SEF) and cognitive performance (CP) have been associated with reduced Alzheimer’s disease (AD) risk, recent evidence highlighted that these factors may have opposite effects on family history of AD (FHAD). METHODS Leveraging data from the UK Biobank (N=448,100) and the All of Us Research Program (N=...

Background and Hypothesis Individuals with schizophrenia (SCZ) suffer from comorbidities that substantially reduce their life expectancy. Socioeconomic inequalities could contribute to many of the negative health outcomes associated with SCZ. Study Design We investigated genome-wide datasets related to SCZ (52 017 cases and 75 889 controls) from t...

To investigate the pleiotropic mechanisms linking brain structure and function to alcohol drinking and tobacco smoking, we integrated genome-wide data generated by the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN; up to 805,431 participants) with information related to 3,935 brain imaging-derived phenotypes (IDPs) available fro...

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European anc...

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships...

Purpose Coding mutations in the Transthyretin (TTR) gene cause a hereditary form of amyloidosis characterized by a complex genotype-phenotype correlation with limited information regarding differences among worldwide populations. Methods We compared 676 diverse individuals carrying TTR amyloidogenic mutations (rs138065384, Phe44Leu; rs730881165, A...

Background and Aims Experiencing a traumatic event may lead to Posttraumatic Stress Disorder (PTSD), including symptoms such as flashbacks and hyperarousal. Individuals suffering from PTSD are at increased risk of cardiovascu- lar disease (CVD), but it is unclear why. This study assesses shared genetic liability and potential causal pathways betwee...

Hearing difficulty (HD) is one of the major health burdens in older adults. While aging-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. We analyzed a large-scale HD genome-wide association study (GWAS; Ntotal = 501,8...

Hair colour variation is influenced by hundreds of positions across the human genome but this genetic contribution has only been narrowly explored. Genome-wide association studies identified single nucleotide polymorphisms (SNPs) influencing hair colour but the biology underlying these associations is challenging to interpret. We report 16 tandem r...

Bipolar disorder (BD) and schizophrenia (SZ) are associated with higher odds of suicide attempt (SA). In this study, we aimed to explore the effect of BD and SZ genetic liabilities on SA, also considering the contribution of behavioral traits, socioeconomic factors, and substance use disorders. Leveraging large-scale genome-wide association data fr...

To investigate assortative mating (AM), participation bias and socioeconomic status (SES) with respect to the genetics of behavioural and psychiatric traits, we estimated AM signatures using gametic phase disequilibrium and within-spouses and within-siblings polygenic risk score correlation analyses, also performing a SES conditional analysis. The...

Individuals suffering from chronic pain develop substance use disorders (SUDs) more often than others. Understanding the shared genetic influences underlying the comorbidity between chronic pain and SUDs will lead to a greater understanding of their biology. Genome-wide association statistics were obtained from the UK Biobank for multisite chronic...

We leveraged information from more than 1.2 million participants to investigate the genetics of anxiety disorders across five continental ancestral groups. Ancestry-specific and cross-ancestry genome-wide association studies identified 51 anxiety-associated loci, 39 of which are novel. Additionally, polygenic risk scores derived from individuals of...

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (...

The human subcortex is involved in memory and cognition. Structural and functional changes in subcortical regions is implicated in psychiatric conditions. We performed an association study of subcortical volumes using 15,941 tandem repeats (TRs) derived from whole exome sequencing (WES) data in 16,527 unrelated European ancestry participants. We id...

Mental illnesses have a huge impact on individuals, families, and society, so there is a growing need for more efficient treatments. In this context, brain‐computer interface (BCI) technology has the potential to revolutionize the options for neuropsychiatric therapies. However, the development of BCI‐based therapies faces enormous challenges, such...

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by m...

Importance Posttraumatic stress disorder (PTSD) has been reported to be a risk factor for several physical and somatic symptoms. However, the genetics of PTSD and its potential association with medical outcomes remain unclear. Objective To examine disease categories and laboratory tests from electronic health records (EHRs) that are associated wit...

GrimAge acceleration has previously predicted age-related morbidities and mortality. In the current study, we sought to examine how GrimAge is associated with genetic predisposition for systemic inflammation and whether psychosocial factors moderate this association. Military veterans from the National Health and Resilience in Veterans study, which...

Emerging evidence indicates that more nuanced models of posttraumatic stress disorder (PTSD) may better capture the condition’s symptom structure. Recent theoretical and empirical work argue that an 8-factor model of PTSD with separate internally- (e.g. flashbacks) and externally- (e.g. trauma-cue related physiological reactivity) generated intrusi...

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis o...

Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the...

Background and Hypothesis: Individuals with schizophrenia (SCZ) suffer from comorbidities that substantially reduce their life expectancy. Socioeconomic inequalities could contribute to many of the negative health outcomes associated with SCZ. Study Design: We investigated genome-wide datasets related to SCZ (52,017 cases and 75,889 controls) from...

There is a high prevalence of antisocial personality disorder (ASPD) in individuals affected by substance use disorders (SUD). However, there is limited information on the specific patterns of association of ASPD with SUD severity and specific SUD diagnostic criteria. We investigated the association of alcohol, cannabis, cocaine, opioid, and tobacc...

Background: To gain insights into the role of brain structure and function on anxiety (ANX), we conducted a genetically informed investigation leveraging information from ANX genome-wide association studies available from UK Biobank (UKB; N=380,379), FinnGen Program (N=290,361), and Million Veteran Program (MVP; N=199,611) together with UKB genome-...

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ance...

Background: Understanding the interplay between psychosocial factors and polygenic risk scores (PRS) may help elucidate the biopsychosocial etiology of high alcohol consumption (HAC). This study examined the psychosocial moderators of HAC, determined by polygenic risk in a 10-year longitudinal study of US military veterans. We hypothesized that po...

Background: Hearing difficulty (HD) is one of the major health burdens in older adults. While aging-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. Methods: We analyzed a large-scale HD genome-wide association study...

Bipolar disorder (BD) and schizophrenia (SZ) are associated with higher odds of suicide attempt (SA). In this study, we aimed to explore the effect of BD and SZ genetic liabilities on SA, also considering the contribution of behavioral traits, socioeconomic factors, and substance use disorders. Leveraging large-scale genome-wide association data fr...

Background Anxiety disorders are associated with decreased heart rate variability (HRV), but the underlying mechanisms remain elusive. Methods We selected individuals with whole-genome sequencing, Fitbit, and electronic health record data (N=920; 61,333 data points) from the All of Us Research Program. Anxiety PRS were derived with PRS-CS after me...

Background: While COVID-19 outcomes are associated with increased anxiety, individuals affected by anxiety disorders are more likely to develop severe COVID-19 outcomes. Methods: We used genome-wide data from UK Biobank (up to 420,531 participants), FinnGen Project (up to 329,077 participants), Million Veteran Program (175,163 participants), and CO...

To investigate the polygenicity of complex traits in populations of East Asian (EAS) and European (EUR) descents, we leveraged genome-wide data from Biobank Japan, UK Biobank, and FinnGen cohorts. Specifically, we analyzed up to 215 outcomes related to 18 health domains, assessing their polygenic architecture via descriptive statistics, such as the...

To characterize polysubstance addiction (PSA) patterns of cocaine use disorder (CoUD), we performed a latent class analysis (LCA) in 7,989 participants with a lifetime DSM-5 diagnosis of CoUD. This analysis identified three PSA subgroups among CoUD participants (i.e., low, 17%; intermediate, 38%; high, 45%). While these subgroups varied by age, sex...

Genome-wide association studies (GWAS) have underrepresented individuals from non-European populations, impeding progress in characterizing the genetic architecture and consequences of health and disease traits. To address this, we present a population-stratified phenome-wide GWAS followed by a multi-population meta-analysis for 2,068 traits derive...

To investigate the polygenicity of complex traits in populations of East Asian (EAS) and European (EUR) descents, we leveraged genome-wide data from Biobank Japan, UK Biobank, and FinnGen cohorts. Specifically, we analyzed up to 215 outcomes related to 18 health domains, assessing their polygenic architecture via descriptive statistics, such as the...

Background The Million Veteran Program (MVP) participants represent 100 years of US history, including significant social and demographic changes over time. Our study assessed two aspects of the MVP: (i) longitudinal changes in population diversity and (ii) how these changes can be accounted for in genome-wide association studies (GWAS). To investi...

Background Hearing problems (HP) in adults are common and are associated with several comorbid conditions. Its prevalence increases with age, reflecting the cumulative effect of environmental factors and genetic predisposition. Although several risk loci have been already identified, HP biology and epidemiology are still insufficiently investigated...

Endometriosis is a chronic gynecologic disease that causes pelvic pain and is often seen in association with depression and anxiety. The association with these mental health conditions was previously linked to chronic pain, although some evidence suggests this is not the sole factor. A genetic correlation has shown a potential causal effect of depr...

Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n < 11,000) lacking in diversity, which may limit the generalizability of their findings. We present data that partially support this hypothesis from three large cohorts of diverse ancestries, t...

The integration of multi-omics information (e.g., epigenetics and transcriptomics) can be useful for interpreting findings from genome-wide association studies (GWAS). It has been suggested that multi-omics could circumvent or greatly reduce the need to increase GWAS sample sizes for novel variant discovery. We tested whether incorporating multi-om...