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Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals.

ABSTRACT: Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with brain tissue and single cell gene expression data to identify tissues and cell types associated with intelligence. GWAS data for IQ (N?=?78,308) were meta-analyzed with a study comparing 1247 individuals with mean IQ ~170 to 8185 controls. Genes associated with intelligence implicate pyramidal neurons of the somatosensory cortex and CA1 region of the hippocampus, and midbrain embryonic GABAergic neurons. Tissue-specific analyses find the most significant enrichment for frontal cortex brain expressed genes. These results suggest specific neuronal cell types and genes may be involved in intelligence and provide new hypotheses for neuroscience experiments using model systems.

SUBMITTER: Coleman JRI

PROVIDER: S-EPMC6330082 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals.

Coleman Jonathan R I JRI Bryois Julien J Gaspar Héléna A HA Jansen Philip R PR Savage Jeanne E JE Skene Nathan N Plomin Robert R Muñoz-Manchado Ana B AB Linnarsson Sten S Crawford Greg G Hjerling-Leffler Jens J Sullivan Patrick F PF Posthuma Danielle D Breen Gerome G

Molecular psychiatry 20180308 2

Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with brain tissue and single cell gene expression data to identify tissues and cell types associated with intelligence. GWAS data for IQ (N = 78,308) were meta-analyzed with a study comp ...[more]

PMID: 29520040

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Project description:ImportanceThe genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood.ObjectiveTo explore the genetic basis of BD in the Han Chinese population.Design, setting, and participantsA genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020.Main outcomes and measuresSingle-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association.ResultsThe Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956).Conclusions and relevanceThis GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

Dataset Information

Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals.

Publications

Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals.

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