ArticleGenome medicine2021
Integration of genetic, transcriptomic, and clinical data provides insight into 16p11.2 and 22q11.2 CNV genes.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Identifying BMI-associated genes via a genome-wide multi-omics integrative approach using summary data.Human molecular genetics · 2024Pooled it
- CRISPR-Enabled functional genomics in hPSCs-derived neural models for autism spectrum disorder.Metabolic brain disease · 2026Review
- Advancing risk gene discovery across the allele frequency spectrum.HGG advances · 2026Review
- Shared genetic architecture of schizophrenia and Alzheimer's disease and related dementias implicates 16p11.2 and lifespan brain vulnerability.Molecular psychiatry · 2026Article
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- Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance inMicrobial cell (Graz, Austria) · 2026Article
- Identification of potential therapeutic targets for idiopathic pulmonary fibrosis: an integrated multiomics analysis.Frontiers in immunology · 2026Article
- Two genes, one culprit - a functional candidate validation of a SPATA7 deletion in dogs with day blindness/retinal degeneration.PLoS genetics · 2025Article
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- Integrating genetic and transcriptomic data to identify genes underlying obesity risk loci.International journal of obesity (2005) · 2025Article
- Identification and validation of diagnostic alternative splicing events in tumor-educated platelets for non-small cell lung cancer in patients with ground-glass opacity: a multicenter study.Translational lung cancer research · 2025Article
- Neurological Insights into 16p11.2- And 22q11.2-Related Disorders: A Mini-Review.Current genomics · 2025Review
- Downstream transcription promotes human recurrent CNV associated AT-rich sequence mediated genome rearrangements in yeast.iScience · 2024Article
- The pleiotropic spectrum of proximal 16p11.2 CNVs.American journal of human genetics · 2024Review
- Integration of multi-omics summary data reveals the role of N6-methyladenosine in neuropsychiatric disorders.Molecular psychiatry · 2024Article
- SCARF2 is a target for chronic obstructive pulmonary disease: Evidence from multi-omics research and cohort validation.Aging cell · 2024Article
- Concurrent de novo MACF1 mutation and inherited 16p13.11 microduplication in a preterm newborn with hypotonia, joint hyperlaxity and multiple congenital malformations: a case report.BMC pediatrics · 2024Article
- Schizophrenia in the Context of Neurodevelopmental Disorders in 16p12.2 Chromosomal Deletion: A Case Report.Indian journal of psychological medicine · 2024Article
- Dynamic proximity interaction profiling suggests that YPEL2 is involved in cellular stress surveillance.Protein science : a publication of the Protein Society · 2024Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDeletions and duplications of the multigenic 16p11.2 and 22q11.2 copy number variant (CNV) regions are associated with brain-related disorders including schizophrenia, intellectual disability, obesity, bipolar disorder, and autism spectrum disorder (ASD). The contribution of individual CNV genes to each of these identified phenotypes is unknown, as well as the contribution of these CNV genes to other potentially subtler health implications for carriers. Hypothesizing that DNA copy number exerts most effects via impacts on RNA expression, we attempted a novel in silico fine-mapping approach in non-CNV carriers using both GWAS and biobank data.
methodsWe first asked whether gene expression level in any individual gene in the CNV region alters risk for a known CNV-associated behavioral phenotype(s). Using transcriptomic imputation, we performed association testing for CNV genes within large genotyped cohorts for schizophrenia, IQ, BMI, bipolar disorder, and ASD. Second, we used a biobank containing electronic health data to compare the medical phenome of CNV carriers to controls within 700,000 individuals in order to investigate the full spectrum of health effects of the CNVs. Third, we used genotypes for over 48,000 individuals within the biobank to perform phenome-wide association studies between imputed expressions of individual 16p11.2 and 22q11.2 genes and over 1500 health traits.
resultsUsing large genotyped cohorts, we found individual genes within 16p11.2 associated with schizophrenia (TMEM219, INO80E, YPEL3), BMI (TMEM219, SPN, TAOK2, INO80E), and IQ (SPN), using conditional analysis to identify upregulation of INO80E as the driver of schizophrenia, and downregulation of SPN and INO80E as increasing BMI. We identified both novel and previously observed over-represented traits within the electronic health records of 16p11.2 and 22q11.2 CNV carriers. In the phenome-wide association study, we found seventeen significant gene-trait pairs, including psychosis (NPIPB11, SLX1B) and mood disorders (SCARF2), and overall enrichment of mental traits.
conclusionsOur results demonstrate how integration of genetic and clinical data aids in understanding CNV gene function and implicates pleiotropy and multigenicity in CNV biology.
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