69. Cadm2 Is Implicated in Impulsive Personality and Numerous Other Traits by Genome- And Phenome-Wide Association Studies in Humans, With Further Support From Studies of Cadm2 Mutant Mice

Sanchez‐Roige, Sandra; Jennings, Mariela V; Thorpe, Hayley H. A.; Mallari, Jazlene; Werf, Lieke C van der; Bianchi, Sevim B; Mallard, Travis T.; Watters, Katherine; Biederer, Thomas; Elson, Sarah L.; Fontanillas, Pierre; Khokhar, Jibran Y.; Young, Jared W.; Palmer, Abraham A.

doi:10.1016/j.euroneuro.2022.07.156

Cited by 5 publications

(20 citation statements)

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“…As noted, the present study is the first to investigate the latent genetic architecture of dual-systems models using molecular genetic data, and the first of any type to investigate the genetic architecture of an urgency and (lack of) self-control dual-systems model. Thus, while prior studies have examined genetic correlations amongst IPTs using molecular genetic approaches (e.g., Sanchez-Roige et al, 2019, 2022), investigations of the latent genetic architecture underlying dual-systems models more specifically are limited to a small number of behavior genetic studies (Ellingson et al, 2013; 2018; Harden et al, 2017), and as a result, the findings from the present study represent a novel extension of this prior work.…”

Section: Discussionmentioning

confidence: 90%

“…The current study is not without limitations. First, limited sample sizes likely hindered analyses of the (lack of) self-control and urgency traits, demonstrating the need for larger IPT GWAS (e.g., Becker et al, 2021; Sanchez-Roige et al, 2022). Second, and equally important, is the exclusion of non-European ancestry samples from the present study.…”

Section: Discussionmentioning

confidence: 99%

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Dual-systems models of the genetic architecture of impulsive personality traits: Neurogenetic evidence of distinct but related factors

Miller¹,

Gizer

2023

Preprint

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Background: Dual-systems models provide a parsimonious framework for understanding the interplay between cortical and subcortical brain regions relevant to impulsive personality traits (IPTs) and their associations with psychiatric disorders. Despite recent developments in multivariate analysis of genome-wide association studies (GWAS), molecular genetic investigations of these models have not been conducted. Methods: Using extant IPT GWAS, we conducted confirmatory genomic structural equation models (GenomicSEM) to empirically evaluate dual-systems models of the genetic architecture of IPTs. Genetic correlations between results of multivariate GWAS of dual-systems factors and GWAS of relevant cortical and subcortical neuroimaging phenotypes (regional/structural volume, cortical surface area, cortical thickness) were calculated and compared. Results: Evaluation of GenomicSEM model fit indices for dual-systems models suggested that these models highlight important sources of shared and unique genetic variance between top-down and bottom-up constructs. Specifically, a dual-systems genomic model consisting of sensation seeking and lack of self-control factors demonstrated distinct but related sources of genetic influences (rg=.60). Genetic correlation analyses provided evidence of differential associations between dual-systems factors and cortical neuroimaging phenotypes (e.g., lack of self-control negatively associated with cortical thickness, sensation seeking positively associated with cortical surface area). However, no significant associations were observed for subcortical phenotypes inconsistent with hypothesized functional localization of dual-systems constructs. Conclusions: Dual-systems models of the genetic architecture of IPTs tested here demonstrate evidence of shared and unique genetic influences and associations with relevant neuroimaging phenotypes. These findings emphasize potential advantages in utilizing dual-systems models to study genetic influences for IPTs and transdiagnostic associations with psychiatric disorders.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Dual-systems models of the genetic architecture of impulsive personality traits: Neurogenetic evidence of distinct but related factors

Miller¹,

Gizer

2023

Preprint

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“…Among phenotypes previously suggested to be genetically correlated with impulsivity, 11,13,15 we prioritized ADHD, 19 AUDIT total score, 35 smoking 36 (including cessation, initiation, cigarettes per day), cannabis use disorder (CUD), 37 externalizing, 23 neuroticism, 38 general risk tolerance, 39 body mass index (BMI), 40 and educational attainment (EA) 25 . The rationale is based on selecting behavioral traits that are relevant to the non‐clinical sample comprised of adults while controlling the type I error rate under multiple comparisons.…”

Section: Methodsmentioning

confidence: 99%

“…As a result, these GWASs are increasingly generating robust genetic signals at the individual variant level as well as in the form of a genome‐wide polygenic risk score (PRS), which combines association signals into an aggregated variable additively. As compared with individual genetic variants, PRSs provide another potentially powerful tool to characterize the genetic basis of impulsivity phenotypes by leveraging their established SNP‐based heritability and genetic correlation with related traits 11,13,15 . However, no studies have investigated the implications of these estimated heritability and genetic correlations for out‐of‐sample prediction.…”

Section: Introductionmentioning

confidence: 99%

Leveraging related health phenotypes for polygenic prediction of impulsive choice, impulsive action, and impulsive personality traits in 1534 European ancestry community adults

Deng

Belisario

Gray

et al. 2023

Genes Brain and Behavior

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Impulsivity refers to a number of conceptually related phenotypes reflecting self‐regulatory capacity that are considered promising endophenotypes for mental and physical health. Measures of impulsivity can be broadly grouped into three domains, namely, impulsive choice, impulsive action, and impulsive personality traits. In a community‐based sample of ancestral Europeans (n = 1534), we conducted genome‐wide association studies (GWASs) of impulsive choice (delay discounting), impulsive action (behavioral inhibition), and impulsive personality traits (UPPS‐P), and evaluated 11 polygenic risk scores (PRSs) of phenotypes previously linked to self‐regulation. Although there were no individual genome‐wide significant hits, the neuroticism PRS was positively associated with negative urgency (adjusted R2 = 1.61%, p = 3.6 × 10−7) and the educational attainment PRS was inversely associated with delay discounting (adjusted R2 = 1.68%, p = 2.2 × 10−7). There was also evidence implicating PRSs of attention‐deficit/hyperactivity disorder, externalizing, risk‐taking, smoking cessation, smoking initiation, and body mass index with one or more impulsivity phenotypes (adjusted R2s: 0.35%–1.07%; FDR adjusted ps = 0.05–0.0006). These significant associations between PRSs and impulsivity phenotypes are consistent with established genetic correlations. The combined PRS explained 0.91%–2.46% of the phenotypic variance for individual impulsivity measures, corresponding to 8.7%–32.5% of their reported single‐nucleotide polymorphism (SNP)‐based heritability, suggesting a non‐negligible portion of the SNP‐based heritability can be recovered by PRSs. These results support the predictive validity and utility of PRSs, even derived from related phenotypes, to inform the genetics of impulsivity phenotypes.

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“…Intriguingly, in the context of this discussion, genes found in the most restrictively defined lists of deserts of introgression in modern human genomes (regions of the genome depleted of introgressed alleles from neanderthals/denisovans) (Reher, 2021), such as CADM2, have been linked to personality traits like risk-taking behavior, impulsivity, addiction (Pasman et al, 2022;Sanchez-Roige et al, 2022). (Similar signals have been associated with other genes in introgression deserts such as CADPS2 or FOXP2 (Sanchez-Roige et al, 2022).…”

Section: Signals From Comparative (Paleo)genomicsmentioning

confidence: 99%

Loquens : A characterization of “Hunter-Gatherers of Words”

Boeckx¹

2022

Preprint

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This paper makes three interconnected claims: (i) the "human condition" cannot be captured by evolutionary narratives that reduce it to a recent 'cognitive modernity', nor by narratives that eliminates all cognitive differences between us and out closest extinct relatives, (ii) signals from paleogenomics, especially coming from deserts of introgression but also from signatures of positive selection point to the importance of mutations that may underlie temperamental differences, which impact cultural evolutionary trajectories in specific ways, and (iii) these trajectories in turn affect the language phenotypes. In particular, they influence the development of symbolic systems and the flexible ways in which symbols combine.

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69. Cadm2 Is Implicated in Impulsive Personality and Numerous Other Traits by Genome- And Phenome-Wide Association Studies in Humans, With Further Support From Studies of Cadm2 Mutant Mice

Cited by 5 publications

References 0 publications

Dual-systems models of the genetic architecture of impulsive personality traits: Neurogenetic evidence of distinct but related factors

Dual-systems models of the genetic architecture of impulsive personality traits: Neurogenetic evidence of distinct but related factors

Leveraging related health phenotypes for polygenic prediction of impulsive choice, impulsive action, and impulsive personality traits in 1534 European ancestry community adults

Loquens : A characterization of “Hunter-Gatherers of Words”

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