GeneSet Information

Tier IV GS410552 • H-MAGMA results for genes in adult brain tissue implicated in GWAS of externalizing factor_pvalue

DESCRIPTION:

"We amassed a set of phenotype-specific GWAS summary statistics for different externalizing phenotypes, either by collecting existing results or by performing GWAS in UK Biobank (UKB) (Supplementary Information section 2). The multivariate method “genomic structural equation modelling” (Genomic SEM) was applied on a subset of the summary statistics (N = 53,293–1,251,809) deemed adequately heritable and statistically powered, in order to estimate a series of model specifications representing different genetic factor structures (Supplementary Information section 3). The best-fitting and most parsimonious solution (“the preferred model specification”) specified a single common genetic factor with seven indicator phenotypes (which we hereafter refer to as “the latent genetic externalizing factor”, or simply, “the externalizing factor”). The 7 phenotypes eventually used to estimate the latent genetic externalizing factor were (1) ADHD, (2) age at first sexual intercourse (FSEX), (3) problematic alcohol use (ALCP), (4) lifetime cannabis use (CANN), (5) lifetime smoking initiation (SMOK), (6) general risk tolerance (RISK), and (7) number of sexual partners (NSEX). We used an extension of MAGMA v1.08, “Hi-C coupled MAGMA” or “H-MAGMA” (version June 14, 2019), to assign non-coding (intergenic and intronic) SNPs to cognate genes based on their chromatin interactions. Exonic and promoter SNPs were assigned to genes based on physical position. We used four Hi-C datasets derived from adult brain, fetal brain, and iPSC derived neurons and astrocytes. We evaluated Bonferroni corrected P-value thresholds, adjusted for multiple testing within each analysis (one-sided P < 9.84×10–7). Displaying genes with P value less than 1E–5. From supplementary table 17."

LABEL:

H-MAGMA genes in adult brain from EXT GWAS_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

1997

DATE ADDED:

2025-02-14

DATE UPDATED:

2025-06-20

SPECIES:

AUTHORS:

Richard Karlsson Linnér, Travis T Mallard, Peter B Barr, Sandra Sanchez-Roige, James W Madole, Morgan N Driver, Holly E Poore, Ronald de Vlaming, Andrew D Grotzinger, Jorim J Tielbeek, Emma C Johnson, Mengzhen Liu, Sara Brin Rosenthal, Trey Ideker, Hang Zhou, Rachel L Kember, Joëlle A Pasman, Karin J H Verweij, Dajiang J Liu, Scott Vrieze, , Henry R Kranzler, Joel Gelernter, Kathleen Mullan Harris, Elliot M Tucker-Drob, Irwin D Waldman, Abraham A Palmer, K Paige Harden, Philipp D Koellinger, Danielle M Dick

TITLE:

Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction.

JOURNAL:

Nature neuroscience Oct 2021, Vol 24, pp. 1367-1376

ABSTRACT:

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates. PUBMED: 34446935
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Annotation Information

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Social Control, Formal (D012926)
Clinical Coding (D059019)
Indicators and Reagents (D007202)
Behavior (D001519)
Solutions (D012996)
HIV Infections (D015658)
Substance-Related Disorders (D019966)
Smoking (D012907)
Astrocytes (D001253)
Opioid-Related Disorders (D009293)
Suicide (D013405)
Attention (D001288)
Attention Deficit Disorder with Hyperactivity (D001289)
Neurons (D009474)
Risk Factors (D012307)
Criminals (D057237)
Phenotype (D010641)
Genetic Loci (D056426)
Nervous System (D009420)
Unemployment (D014478)
Infection (D007239)
Sexual Partners (D012747)
Biological Specimen Banks (D018070)
Antisocial Personality Disorder (D000987)
Chromatin (D002843)
Cannabis (D002188)
Polymorphism, Single Nucleotide (D020641)
Association (D001244)
Analgesics, Opioid (D000701)
nervous system (MA:0000016)
hyperactivity (MP:0001399)
biological regulation (GO:0065007)
nervous system development (GO:0007399)
chromatin (GO:0000785)
system development (GO:0048731)
developmental process (GO:0032502)
Biostatistics (EDAM_topic:2269)
Structure analysis (EDAM_topic:0081)
Electron microscopy (EDAM_topic:0611)
Pathways, networks and models (EDAM_topic:0602)
Genotype and phenotype (EDAM_topic:0625)
advanced glycation end-product (CHEBI:84123)
indicator (CHEBI:47867)
L-selenomethionine residue (CHEBI:30019)
Hyperactivity (HP:0000752)
attention deficit hyperactivity disorder (DOID:1094)
smoking initiation (EFO:0005670)
induced pluripotent stem cell (EFO:0004905)
smoking behavior (EFO:0004318)
attention deficit hyperactivity disorder (EFO:0003888)
HIV infection (EFO:0000764)
Cannabis use (EFO:0007585)
obsolete_brain (EFO:0000302)
nicotine dependence (EFO:0003768)
phenotype (EFO:0000651)
obsolete_induced pluripotent stem cell (EFO:0005739)
nervous system (UBERON:0001016)
anatomical system (UBERON:0000467)
adult organism (UBERON:0007023)
adult cerebral ganglion (UBERON:6110636)

Gene List • 1997 Genes

Genes in threshold: 1997

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