Biology subjects

Elson, S. L.

Publications and source records attributed to Elson, S. L..

6 recordsLinked to original sources

bioRxiv2020

The Latent Genetic Structure of Impulsivity and its Relation to Internalizing Psychopathology

Factor analyses suggest that impulsivity traits that capture tendencies to act prematurely or take risks tap partially distinct constructs. We applied genomic structure equation modeling to evaluate the genetic factor structure of two well-established impulsivity questionnaires, using published genome-wide association study statistics from up to 22,861 participants. We also tested the hypotheses that delay discounting would be genetically separable from other impulsivity factors, and that emotionally-triggered facets of impulsivity (urgency) would be those most strongly genetically correlated with an internalizing latent factor. A five-factor model best fit the impulsivity data. Delay discounting was genetically distinct from these five factors. As expected, the two urgency subscales were most strongly related to an Internalizing Psychopathology latent factor. These findings provide empirical genetic evidence that impulsivity can be disarticulated into distinct categories of differential relevance for internalizing psychopathology. They also demonstrate how measured genetic markers can be used to inform theories of psychology/personality.

genetics↗

bioRxiv2019

Genetic risk for major depressive disorder and loneliness in gender-specific associations with coronary artery disease

ImportanceEpidemiological evidence indicates that major depressive disorder (MDD) and loneliness both reduce life expectancies, but mechanisms underlying the excess morbidity are unclear. Electronic health records (EHRs) linked to genetic data offer new opportunities to address this knowledge gap.\n\nObjectiveTo determine the medical morbidity pattern associated with genetic risk factors for MDD and loneliness, two common psychological traits with adverse health outcomes.\n\nDesignPhenome-wide association study using EHRs spanning 1990 to 2017 from the Vanderbilt University Medical Center biobank, BioVU. Top associations with coronary artery disease (CAD) were replicated in the Atherosclerosis Risk in Communities (ARIC) cohort.\n\nSettingHospital-based EHR study, with replication in a population-based cohort study.\n\nParticipants18,385 genotyped adult patients in BioVU. Replication in ARIC included 7,197 genotyped participants. All participants were of European ancestry.\n\nExposuresPolygenic scores for MDD and loneliness were developed for each individual using previously published meta-GWAS summary statistics.\n\nMain Outcomes and MeasuresThe phenome-wide association study included 882 clinical diagnoses ascertained via billing codes in the EHR. ARIC included 1598 incident CAD cases.\n\nResultsBioVU patients had a median EHR length of 9.91 years. In the phenome-wide association study, polygenic scores for MDD and loneliness were significantly associated with psychiatric and cardiac phenotypes. Targeted analyses of CAD in 3,893 cases and 4,197 controls in BioVU found odds ratios of 1.11 (95% CI, 1.04-1.18; P=8.43x10-4) and 1.13 (95% CI, 1.07-1.20; P=4.51x10-6) per 1-SD increase in the polygenic scores for MDD and loneliness, respectively. Comparable hazard ratios in ARIC were 1.07 (95% CI, 0.99-1.14; P=0.07) and 1.07 (1.01-1.15; P=0.03). Across both studies, the increased risk persisted in women after adjusting for multiple conventional risk factors, a polygenic score for CAD, and psychiatric symptoms (available in BioVU). Controlling for genetic risk factors shared between MDD and loneliness, the polygenic score for loneliness conditioned on MDD remained associated with CAD risk, but the polygenic score for MDD conditioned on loneliness did not.\n\nConclusions and RelevanceGenetic risk factors for MDD and loneliness act pleiotropically to increase CAD risk in women. Continued research into the biological and clinical connections between the heart and mind is warranted.

genetics↗

bioRxiv2018

Genome-wide association studies of impulsive personality traits (BIS-11 and UPPSP) and drug experimentation in up to 22,861 adult research participants

BackgroundImpulsive personality traits are complex heritable traits that are governed by frontal-subcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse.\n\nMethodsIn collaboration with the genetics company 23andMe, Inc., we performed several genome-wide association studies (GWAS) on measures of impulsive personality traits (the short version of the UPPSP Impulsive Behavior Scale, and the Barratt Impulsiveness Scale [BIS-11]) and drug experimentation (the number of drug classes an individual has tried in their lifetime) in up to 22,861 male and female adult research participants of European ancestry.\n\nResultsImpulsive personality traits and drug experimentation showed SNP-heritabilities that ranged from 5 to 11%. Genetic variants in the CADM2 locus were significantly associated with the UPPSP Sensation Seeking subscale (P = 8.3 x 10-9, rs139528938) and showed a suggestive association with drug experimentation (P = 3.0 x 10-7, rs2163971; r2 = 0.68 with rs139528938); CADM2 has been previously associated with measures of risky behaviors and self-reported risk tolerance, cannabis initiation, alcohol consumption, as well as information speed processing, body mass index (BMI) variation and obesity. Furthermore, genetic variants in the CACNA1I locus were significantly associated with the UPPSP Negative Urgency subscale (P = 3.8 x 10-8, rs199694726). Multiple subscales from both UPPSP and BIS showed strong genetic correlations (>0.5) with drug experimentation and other substance use traits measured in independent cohorts, including smoking initiation, and lifetime cannabis use. Several UPPSP and BIS subscales were genetically correlated with attention-deficit/hyperactivity disorder (rg = 0.30-0.51, p < 8.69 x 10-3), supporting their validity as endophenotypes.\n\nConclusionsOur findings demonstrate a role for common genetic contributions to individual differences in impulsivity. Furthermore, our study is the first to provide a genetic dissection of the relationship between different types of impulsive personality traits and various psychiatric disorders.

genetics↗

bioRxiv2018

Genome-wide association analysis of lifetime cannabis use (N=184,765) identifies new risk loci, genetic overlap with mental health, and a causal influence of schizophrenia on cannabis use

Cannabis use is a heritable trait [1] that has been associated with adverse mental health outcomes. To identify risk variants and improve our knowledge of the genetic etiology of cannabis use, we performed the largest genome-wide association study (GWAS) meta-analysis for lifetime cannabis use (N=184,765) to date. We identified 4 independent loci containing genome-wide significant SNP associations. Gene-based tests revealed 29 genome-wide significant genes located in these 4 loci and 8 additional regions. All SNPs combined explained 10% of the variance in lifetime cannabis use. The most significantly associated gene, CADM2, has previously been associated with substance use and risk-taking phenotypes [2-4]. We used S-PrediXcan to explore gene expression levels and found 11 unique eGenes. LD-score regression uncovered genetic correlations with smoking, alcohol use and mental health outcomes, including schizophrenia and bipolar disorder. Mendelian randomisation analysis provided evidence for a causal positive influence of schizophrenia risk on lifetime cannabis use.

genetics↗

bioRxiv2017

Genome-wide association study of Alcohol Use Disorder Identification Test (AUDIT) scores in 20,328 research participants of European ancestry

Genetic factors contribute to the risk for developing alcohol use disorder (AUD). In collaboration with the genetics company 23andMe, Inc., we performed a genome-wide association (GWAS) study of the Alcohol Use Disorder Identification Test (AUDIT), an instrument designed to screen for alcohol misuse over the past year. Our final sample consisted of 20,328 research participants of European ancestry (55.3% females; mean age = 53.8, SD = 16.1) who reported ever using alcohol. Our results showed that the chip-heritability of AUDIT score, when treated as a continuous phenotype, was 12%. No loci reached genome-wide significance. The gene ADH1C, which has been previously implicated in AUD, was among our most significant associations (4.4 x 10-7; rs141973904). We also detected a suggestive association on chromosome 1 (2.1 x 10-7; rs182344113) near the gene KCNJ9, which has been implicated in mouse models of high ethanol drinking. Using LD score regression, we identified positive genetic correlations between AUDIT score and AUD, high alcohol consumption, and cigarette smoking. We also observed an unexpected positive genetic correlation between AUDIT and educational attainment, and additional unexpected negative correlations with BMI/obesity and attention-deficit/hyperactivity disorder (ADHD). We conclude that conducting a genetic study using data from a population unselected for AUD and responding to an online questionnaire may represent a cost-effective strategy for elucidating the etiology of AUD.

genetics↗

bioRxiv2017

Genetics of the Research Domain Criteria (RDoC): genome-wide association study of delay discounting

Delay discounting (DD), which is the tendency to discount the value of delayed versus current rewards, is elevated in a constellation of diseases and behavioral conditions. We performed a genome-wide association study of DD using 23,127 research participants of European ancestry. The most significantly associated SNP was rs6528024 (P = 2.40 x 10-8), which is located in an intron of the gene GPM6B. We also showed that 12% of the variance in DD was accounted for by genotype, and that the genetic signature of DD overlapped with attention-deficit/hyperactivity disorder, schizophrenia, major depression, smoking, personality, cognition, and body weight.

genetics↗