Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry

Sanchez‐Roige, Sandra; Fontanillas, Pierre; Elson, Sarah L.; Pandit, Anita; Schmidt, Ellen M.; Forster, Johanna; Abecasis, Gonçalo R.; Gray, Joshua C.; Wit, Harriet de; Davis, Lea K.; MacKillop, James; Palmer, Abraham A.

doi:10.1101/146936

Cited by 31 publications

(65 citation statements)

References 20 publications

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“…In economics, non-cognitive influences on achievement and health are often studied in relation to decisionmaking preferences [35][36][37][38] . NonCog was genetically correlated with higher levels of comfort with risk-taking 39 (risk tolerance rg=.10 (SE=.03)) and willingness to forego immediate gratification in favor of a larger reward at a later time 40 (delay discounting rg=-.52 (SE=.08)). In contrast,…”

Section: Phenotypic Annotation II Exploring Genetic Correlates Of Thmentioning

confidence: 99%

Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

Demange

Malanchini

Mallard

et al. 2020

Preprint

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Educational attainment (EA) is influenced by cognitive abilities and by other characteristics and traits. However little is known about the genetic architecture of these "non-cognitive" contributions to EA. Here, we use Genomic Structural Equation Modelling and results of prior genome-wide association studies (GWASs) of EA (N = 1,131,881) and cognitive test performance (N = 257,841) to estimate SNP associations with variation in EA that is independent of cognitive ability. We identified 157 genome-wide significant loci and a polygenic architecture accounting for 57% of genetic variance in EA. Phenotypic and biological annotation revealed that (1) both cognitive and non-cognitive contributions to EA were genetically correlated with socioeconomic success and longevity; and (2) non-cognitive contributions to EA were related to personality, decision making, risk-behavior, and increased risk for psychiatric disorders; (3) non-cognitive and cognitive contributions to EA were enriched in the same tissues and cell types, but (4) showed different associations with graymatter neuroimaging phenotypes.

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Section: Phenotypic Annotation II Exploring Genetic Correlates Of Thmentioning

confidence: 99%

Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

Demange

Malanchini

Mallard

et al. 2020

Preprint

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“…Recruitment occurred over an approximately four-month period in 2015. This sample has been extensively described elsewhere (27,28). Sociodemographic details are described in the Supplementary Table 1.…”

Section: Samplementioning

confidence: 99%

“…We have previously reported a full description of these methods (27). DNA extraction and genotyping were performed on saliva samples by CLIA-certified and CAP-accredited clinical laboratories of Laboratory Corporation of America.…”

Section: Genotyping Quality Control and Imputationmentioning

confidence: 99%

“…Sanchez-Roige S 6 GWAS analyses were performed using the 23andMe internal pipeline, which we have previously described (27). We performed association tests by linear regression (additive model).…”

Section: Genome-wide Association Analysesmentioning

confidence: 99%

“…We used precomputed tissue weights from the Genotype-Tissue Expression (GTEx v6) project database (https://www.gtexportal.org/) as the reference transcriptome dataset. Further details are provided elsewhere (27).…”

Section: Gene-based and Transcriptome-based Analysesmentioning

confidence: 99%

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

Sanchez‐Roige

Fontanillas

Elson

et al. 2018

Preprint

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Background: Impulsive personality traits are complex heritable traits that are governed by frontalsubcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse. Methods:In 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 ) 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. Results: Impulsive 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 × 10 −9 , rs139528938) and showed a suggestive association with drug experimentation (P = 3.0 × 10 −7 , rs2163971; r 2 = 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 × 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. Conclusions: Our 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. Sanchez-Roige S

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Steep Discounting of Future Rewards as an Impulsivity Phenotype: A Concise Review

Levitt

Sanchez‐Roige

Palmer

et al. 2020

Current Topics in Behavioral Neurosciences

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Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry

Cited by 31 publications

References 20 publications

Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

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

Steep Discounting of Future Rewards as an Impulsivity Phenotype: A Concise Review

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