List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Maximal oxygen uptake response. The EFO term maximal oxygen uptake measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.
Authors:
I Ahmetov, N Kulemin, D Popov, V Naumov, E Akimov, Y Bravy, E Egorova, A Galeeva, E Generozov, E Kostryukova, A Larin, Lj Mustafina, E Ospanova, A Pavlenko, L Starnes, P Żmijewski, D Alexeev, O Vinogradova, V Govorun
List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Thyroid hormone levels. The EFO term thyroid stimulating hormone measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.
Authors:
E Porcu, M Medici, G Pistis, CB Volpato, SG Wilson, AR Cappola, SD Bos, J Deelen, M den Heijer, RM Freathy, J Lahti, C Liu, LM Lopez, IM Nolte, JR O'Connell, T Tanaka, S Trompet, A Arnold, S Bandinelli, M Beekman, S Böhringer, SJ Brown, BM Buckley, C Camaschella, AJ de Craen, G Davies, MC de Visser, I Ford, T Forsen, TM Frayling, L Fugazzola, M Gögele, AT Hattersley, AR Hermus, A Hofman, JJ Houwing-Duistermaat, RA Jensen, E Kajantie, M Kloppenburg, EM Lim, C Masciullo, S Mariotti, C Minelli, BD Mitchell, R Nagaraja, RT Netea-Maier, A Palotie, L Persani, MG Piras, BM Psaty, K Räikkönen, JB Richards, F Rivadeneira, C Sala, MM Sabra, N Sattar, BM Shields, N Soranzo, JM Starr, DJ Stott, FC Sweep, G Usala, MM van der Klauw, D van Heemst, A van Mullem, SH Vermeulen, WE Visser, JP Walsh, RG Westendorp, E Widen, G Zhai, F Cucca, IJ Deary, JG Eriksson, L Ferrucci, CS Fox, JW Jukema, LA Kiemeney, PP Pramstaller, D Schlessinger, AR Shuldiner, EP Slagboom, AG Uitterlinden, B Vaidya, TJ Visser, BH Wolffenbuttel, I Meulenbelt, JI Rotter, TD Spector, AA Hicks, D Toniolo, S Sanna, RP Peeters, S Naitza
List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was QRS duration. The EFO term QRS duration was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.
Authors:
DS Evans, CL Avery, MA Nalls, G Li, J Barnard, EN Smith, T Tanaka, AM Butler, SG Buxbaum, A Alonso, DE Arking, GS Berenson, JC Bis, S Buyske, CL Carty, W Chen, MK Chung, SR Cummings, R Deo, CB Eaton, ER Fox, SR Heckbert, G Heiss, LA Hindorff, WC Hsueh, A Isaacs, Y Jamshidi, KF Kerr, F Liu, Y Liu, KK Lohman, JW Magnani, JF Maher, R Mehra, YA Meng, SK Musani, C Newton-Cheh, KE North, BM Psaty, S Redline, JI Rotter, RB Schnabel, NJ Schork, RV Shohet, AB Singleton, JD Smith, EZ Soliman, SR Srinivasan, HA Taylor, DR Van Wagoner, JG Wilson, T Young, ZM Zhang, AB Zonderman, MK Evans, L Ferrucci, SS Murray, GJ Tranah, EA Whitsel, AP Reiner, N Sotoodehnia
Postmortem human brain tissue from the caudate nucleus region of a total of 48 individuals with Alcohol Use Disorder (AUD) and 51 control individuals were taken and RNA extracted from frozen tissue. Sequencing was carried out using the NovaSeq 6000 (Illumina) platform, and gene expression analysis was carried out with respect to AUD and control samples. Gene symbols from Entrez ids are used and Logbase2 FC as provided by the authors are annotated.
Authors:
Lea Zillich, Eric Poisel, Josef Frank, Jerome C Foo, Marion M Friske, Fabian Streit, Lea Sirignano, Stefanie Heilmann-Heimbach, André Heimbach, Per Hoffmann, Franziska Degenhardt, Anita C Hansson, Georgy Bakalkin, Markus M Nöthen, Marcella Rietschel, Rainer Spanagel, Stephanie H Witt
Postmortem human brain tissue from the putamen region of a total of 48 individuals with Alcohol Use Disorder (AUD) and 51 control individuals were taken and RNA extracted from frozen tissue. Sequencing was carried out using the NovaSeq 6000 (Illumina) platform, and gene expression analysis was carried out with respect to AUD and control samples. Gene symbols from Entrez ids are used and Logbase2 FC as provided by the authors are annotated.
Authors:
Lea Zillich, Eric Poisel, Josef Frank, Jerome C Foo, Marion M Friske, Fabian Streit, Lea Sirignano, Stefanie Heilmann-Heimbach, André Heimbach, Per Hoffmann, Franziska Degenhardt, Anita C Hansson, Georgy Bakalkin, Markus M Nöthen, Marcella Rietschel, Rainer Spanagel, Stephanie H Witt
Data from GEO GSE194368 and analyzed using GEO2R, only top gene shown. Authors identified transcriptional adaptations of GR signaling in the amygdala of humans with OUD. Thus, GRs, their coregulators and downstream systems may represent viable therapeutic targets to treat the “stress side” of OUD.
Authors:
Stephanie A Carmack, Janaina C M Vendruscolo, M Adrienne McGinn, Jorge Miranda-Barrientos, Vez Repunte-Canonigo, Gabriel D Bosse, Daniele Mercatelli, Federico M Giorgi, Yu Fu, Anthony J Hinrich, Francine M Jodelka, Karen Ling, Robert O Messing, Randall T Peterson, Frank Rigo, Scott Edwards, Pietro P Sanna, Marisela Morales, Michelle L Hastings, George F Koob, Leandro F Vendruscolo
Data from GEO GSE194368 and analyzed using GEO2R, only top gene shown. Authors identified transcriptional adaptations of GR signaling in the amygdala of humans with OUD. Thus, GRs, their coregulators and downstream systems may represent viable therapeutic targets to treat the “stress side” of OUD.
Authors:
Stephanie A Carmack, Janaina C M Vendruscolo, M Adrienne McGinn, Jorge Miranda-Barrientos, Vez Repunte-Canonigo, Gabriel D Bosse, Daniele Mercatelli, Federico M Giorgi, Yu Fu, Anthony J Hinrich, Francine M Jodelka, Karen Ling, Robert O Messing, Randall T Peterson, Frank Rigo, Scott Edwards, Pietro P Sanna, Marisela Morales, Michelle L Hastings, George F Koob, Leandro F Vendruscolo
Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC. Analyzed using GEO2R (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174409) separately for each brain region, comparing OUD and control samples.
Authors:
Xiangning Xue, Wei Zong, Jill R Glausier, Sam-Moon Kim, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Marianne L Seney, Ryan W Logan
Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC. Analyzed using GEO2R (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174409) separately for each brain region, comparing OUD and control samples.
Authors:
Xiangning Xue, Wei Zong, Jill R Glausier, Sam-Moon Kim, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Marianne L Seney, Ryan W Logan
Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC. Analyzed using GEO2R (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174409) separately for each brain region, comparing OUD and control samples.
Authors:
Xiangning Xue, Wei Zong, Jill R Glausier, Sam-Moon Kim, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Marianne L Seney, Ryan W Logan
List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Parental longevity (combined parental age at death). The EFO term parental longevity was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.
Authors:
LC Pilling, JL Atkins, K Bowman, SE Jones, J Tyrrell, RN Beaumont, KS Ruth, MA Tuke, H Yaghootkar, AR Wood, RM Freathy, A Murray, MN Weedon, L Xue, K Lunetta, JM Murabito, LW Harries, JM Robine, C Brayne, GA Kuchel, L Ferrucci, TM Frayling, D Melzer
Postmortem human brain tissue from the ventral striatum from postmortem human brain tissue with Alcohol Use Disorder (AUD) region of a total of 48 individuals with Alcohol Use Disorder (AUD) and 51 control individuals were taken and RNA extracted from frozen tissue. Sequencing was carried out using the NovaSeq 6000 (Illumina) platform, and gene expression analysis was carried out with respect to AUD and control samples. Gene symbols from Entrez ids are used and Logbase2 FC as provided by the authors are annotated.
Authors:
Lea Zillich, Eric Poisel, Josef Frank, Jerome C Foo, Marion M Friske, Fabian Streit, Lea Sirignano, Stefanie Heilmann-Heimbach, André Heimbach, Per Hoffmann, Franziska Degenhardt, Anita C Hansson, Georgy Bakalkin, Markus M Nöthen, Marcella Rietschel, Rainer Spanagel, Stephanie H Witt
Differentially expressed genes from RPE compared to Normal Retina
Description:
Transcriptome profiling from macular retina and RPE/choroid samples from 27 unrelated eye tissue donors, was performed using RNA-sequencing. Human donor eye collection were obtained from Utah Lions Eye Bank within a 6-hour post-mortem interval and donors aged 60-90 years. Sample types were Normal Retina, Intermediate AMD Retina, Neovascular AMD Retina, Normal macular retina pigment epithelium (RPE), Intermediate AMD RPE, and Neovascular AMD RPE. Age Related Macular Degeneration (AMD) phenotyping was determined using the Age-Related Eye Disease Study (AREDS) severity grading scale, where AREDS category 0/1 was considered normal, AREDS category 3 intermediate AMD, and AREDS category 4b neovascular AMD. Samples from Normal RPE were compared to Normal Retina, and are presented with fold change > 1.5 and and P < 0.05. This gene set was annotated from the Supplementry Table of BioRxiv pre-print paper ‘Patterns of gene expression and allele-specific expression vary among macular tissues and clinical stages of Age-related Macular Degeneration’ by Zhang et.al (2022) doi: https://doi.org/10.1101/2022.12.19.521092
The dataset used in this study (Bulk RNA-Seq) was previously published and can be found at NCBI GEO (GSE182321), this analysis was conducted by GEO2R to compare control and OUD samples, only top differentially expressed genes are reported. To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function.
The dataset used in this study (Bulk RNA-Seq) was previously published and can be found at NCBI GEO (GSE182321), this analysis was conducted by GEO2R to compare control and OUD samples, only top differentially expressed genes are reported. To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function.
Postmortem tissue samples of the dorsolateral prefrontal cortex (DLPFC) from 153 deceased individuals (Mage = 35.4; 62% male; 77% European ancestry). Study groups included 72 brain samples from individuals who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Whole transcriptome RNA-sequencing was used to generate exon counts, and differential expression was tested using limma-voom. Analyses were adjusted for relevant sociodemographic characteristics, technical covariates, and cryptic relatedness using quality surrogate variables. Weighted correlation network analysis and gene set enrichment analyses also were conducted.
Authors:
David W Sosnowski, Andrew E Jaffe, Ran Tao, Amy Deep-Soboslay, Chang Shu, Sarven Sabunciyan, Joel E Kleinman, Thomas M Hyde, Brion S Maher
Postmortem tissue samples of the dorsolateral prefrontal cortex (DLPFC) from 153 deceased individuals (Mage = 35.4; 62% male; 77% European ancestry). Study groups included 72 brain samples from individuals who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Whole transcriptome RNA-sequencing was used to generate exon counts, and differential expression was tested using limma-voom. Analyses were adjusted for relevant sociodemographic characteristics, technical covariates, and cryptic relatedness using quality surrogate variables. Weighted correlation network analysis and gene set enrichment analyses also were conducted.
Authors:
David W Sosnowski, Andrew E Jaffe, Ran Tao, Amy Deep-Soboslay, Chang Shu, Sarven Sabunciyan, Joel E Kleinman, Thomas M Hyde, Brion S Maher
Human induced pluripotent stem cell (iPSC) lines, A and B, derived from two healthy adult male individuals, were used to generate hCOs for RNA-sequencing. Methodone treatment began on Day 9 of organoid culture, the first day of the neural proliferation stage, and concluded at Day 60. Nuclease-free water was used as a vehicular control. Cortical organoids were collected 2 months (60 days) after initiating organoid culture. Each well of hCOs (15–20 organoids) was a separate biological replicate for a given treatment condition (i.e., treated or untreated). RNA was extracted from frozen organoid pellets using the Direct-Zol Miniprep Plus Kit (Zymo, Irvine, CA) according to the manufacturer’s instructions. Samples were multiplexed and sequenced on the Illumina NovaSeq 6000 S4 to produce approximately 100 million, 100 base pair, paired end reads per sample. 3 control and 3 methadone-treated samples were sequenced from cell line A, and 4 control and 4 treated samples from cell line B. Raw fastq file quality assessment and read alignment to the hg19 genome (GRCh37, RefSeq GCF_000001405.13) were performed. Significantly differentially expressed genes (DEGs) were selected based on the confident effect size of their log2(Fold Change) values at FDR<0.05. Genes presented are without cutoffs and were obtained using the GEO2R tool by GW curators (GEO accession: GSE210682).
Authors:
Ila Dwivedi, Andrew B Caldwell, Dan Zhou, Wei Wu, Shankar Subramaniam, Gabriel G Haddad
Human induced pluripotent stem cell (iPSC) lines, A and B, derived from two healthy adult male individuals, were used to generate hCOs for RNA-sequencing. Methodone treatment began on Day 9 of organoid culture, the first day of the neural proliferation stage, and concluded at Day 60. Nuclease-free water was used as a vehicular control. Cortical organoids were collected 2 months (60 days) after initiating organoid culture. Each well of hCOs (15–20 organoids) was a separate biological replicate for a given treatment condition (i.e., treated or untreated). RNA was extracted from frozen organoid pellets using the Direct-Zol Miniprep Plus Kit (Zymo, Irvine, CA) according to the manufacturer’s instructions. Samples were multiplexed and sequenced on the Illumina NovaSeq 6000 S4 to produce approximately 100 million, 100 base pair, paired end reads per sample. 3 control and 3 methadone-treated samples were sequenced from cell line A, and 4 control and 4 treated samples from cell line B. Raw fastq file quality assessment and read alignment to the hg19 genome (GRCh37, RefSeq GCF_000001405.13) were performed. Significantly differentially expressed genes (DEGs) were selected based on the confident effect size of their log2(Fold Change) values at FDR<0.05. Genes presented are without cutoffs and were obtained using the GEO2R tool by GW curators (GEO accession: GSE210682).
Authors:
Ila Dwivedi, Andrew B Caldwell, Dan Zhou, Wei Wu, Shankar Subramaniam, Gabriel G Haddad
DEG methadone human cortical organoids cell line A_pvalue
Description:
Human induced pluripotent stem cell (iPSC) lines, A and B, derived from two healthy adult male individuals, were used to generate hCOs for RNA-sequencing. Methodone treatment began on Day 9 of organoid culture, the first day of the neural proliferation stage, and concluded at Day 60. Nuclease-free water was used as a vehicular control. Cortical organoids were collected 2 months (60 days) after initiating organoid culture. Each well of hCOs (15–20 organoids) was a separate biological replicate for a given treatment condition (i.e., treated or untreated). RNA was extracted from frozen organoid pellets using the Direct-Zol Miniprep Plus Kit (Zymo, Irvine, CA) according to the manufacturer’s instructions. Samples were multiplexed and sequenced on the Illumina NovaSeq 6000 S4 to produce approximately 100 million, 100 base pair, paired end reads per sample. 3 control and 3 methadone-treated samples were sequenced from cell line A, and 4 control and 4 treated samples from cell line B. Raw fastq file quality assessment and read alignment to the hg19 genome (GRCh37, RefSeq GCF_000001405.13) were performed. Significantly differentially expressed genes (DEGs) were selected based on the confident effect size of their log2(Fold Change) values at FDR<0.05. Genes presented are without cutoffs and were obtained using the GEO2R tool by GW curators (GEO accession: GSE210682).
Authors:
Ila Dwivedi, Andrew B Caldwell, Dan Zhou, Wei Wu, Shankar Subramaniam, Gabriel G Haddad
DEG methadone human cortical organoids cell line A_qvalue
Description:
Human induced pluripotent stem cell (iPSC) lines, A and B, derived from two healthy adult male individuals, were used to generate hCOs for RNA-sequencing. Methodone treatment began on Day 9 of organoid culture, the first day of the neural proliferation stage, and concluded at Day 60. Nuclease-free water was used as a vehicular control. Cortical organoids were collected 2 months (60 days) after initiating organoid culture. Each well of hCOs (15–20 organoids) was a separate biological replicate for a given treatment condition (i.e., treated or untreated). RNA was extracted from frozen organoid pellets using the Direct-Zol Miniprep Plus Kit (Zymo, Irvine, CA) according to the manufacturer’s instructions. Samples were multiplexed and sequenced on the Illumina NovaSeq 6000 S4 to produce approximately 100 million, 100 base pair, paired end reads per sample. 3 control and 3 methadone-treated samples were sequenced from cell line A, and 4 control and 4 treated samples from cell line B. Raw fastq file quality assessment and read alignment to the hg19 genome (GRCh37, RefSeq GCF_000001405.13) were performed. Significantly differentially expressed genes (DEGs) were selected based on the confident effect size of their log2(Fold Change) values at FDR<0.05. Genes presented are without cutoffs and were obtained using the GEO2R tool by GW curators (GEO accession: GSE210682).
Authors:
Ila Dwivedi, Andrew B Caldwell, Dan Zhou, Wei Wu, Shankar Subramaniam, Gabriel G Haddad
DEG methadone human cortical organoids cell line B_pvalue
Description:
Human induced pluripotent stem cell (iPSC) lines, A and B, derived from two healthy adult male individuals, were used to generate hCOs for RNA-sequencing. Methodone treatment began on Day 9 of organoid culture, the first day of the neural proliferation stage, and concluded at Day 60. Nuclease-free water was used as a vehicular control. Cortical organoids were collected 2 months (60 days) after initiating organoid culture. Each well of hCOs (15–20 organoids) was a separate biological replicate for a given treatment condition (i.e., treated or untreated). RNA was extracted from frozen organoid pellets using the Direct-Zol Miniprep Plus Kit (Zymo, Irvine, CA) according to the manufacturer’s instructions. Samples were multiplexed and sequenced on the Illumina NovaSeq 6000 S4 to produce approximately 100 million, 100 base pair, paired end reads per sample. 3 control and 3 methadone-treated samples were sequenced from cell line A, and 4 control and 4 treated samples from cell line B. Raw fastq file quality assessment and read alignment to the hg19 genome (GRCh37, RefSeq GCF_000001405.13) were performed. Significantly differentially expressed genes (DEGs) were selected based on the confident effect size of their log2(Fold Change) values at FDR<0.05. Genes presented are without cutoffs and were obtained using the GEO2R tool by GW curators (GEO accession: GSE210682).
Authors:
Ila Dwivedi, Andrew B Caldwell, Dan Zhou, Wei Wu, Shankar Subramaniam, Gabriel G Haddad
DEG methadone human cortical organoids cell line B_qvalue
Description:
Human induced pluripotent stem cell (iPSC) lines, A and B, derived from two healthy adult male individuals, were used to generate hCOs for RNA-sequencing. Methodone treatment began on Day 9 of organoid culture, the first day of the neural proliferation stage, and concluded at Day 60. Nuclease-free water was used as a vehicular control. Cortical organoids were collected 2 months (60 days) after initiating organoid culture. Each well of hCOs (15–20 organoids) was a separate biological replicate for a given treatment condition (i.e., treated or untreated). RNA was extracted from frozen organoid pellets using the Direct-Zol Miniprep Plus Kit (Zymo, Irvine, CA) according to the manufacturer’s instructions. Samples were multiplexed and sequenced on the Illumina NovaSeq 6000 S4 to produce approximately 100 million, 100 base pair, paired end reads per sample. 3 control and 3 methadone-treated samples were sequenced from cell line A, and 4 control and 4 treated samples from cell line B. Raw fastq file quality assessment and read alignment to the hg19 genome (GRCh37, RefSeq GCF_000001405.13) were performed. Significantly differentially expressed genes (DEGs) were selected based on the confident effect size of their log2(Fold Change) values at FDR<0.05. Genes presented are without cutoffs and were obtained using the GEO2R tool by GW curators (GEO accession: GSE210682).
Authors:
Ila Dwivedi, Andrew B Caldwell, Dan Zhou, Wei Wu, Shankar Subramaniam, Gabriel G Haddad
"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."
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
Sig. H-MAGMA genes in adult brain from EXT GWAS_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. Genes with significant corrected p-values shown here (one-sided P < 9.84×10–7). From supplementary table 17."
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
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