120 lead SNPs (88 independent loci) for the tobacco use disorder cross-ancestry meta-analysis ("TUD-multi"). The primary multi-ancestry meta-analysis of 20,801,211 imputed SNPs (lambda λGC=1.141, Figure 2) was performed on seven cohorts from four U.S. biobanks, comprising 653,790 individuals with TUD phecode data available, with 75.71% EUR, 17.50% AA, and 6.79% LA. We defined cases as patients who received at least two TUD ICD-9 or −10 codes (corresponding to the phecode definition) in their medical records, and controls as patients who had no TUD diagnosis codes. All genome-wide significant loci had been reported by prior smoking GWAS (Supplementary Table 7), including aspects of smoking initiation (88/88), age of initiation (14/88), consumption (38/88), cessation (48/88) and nicotine dependence (1/88; Supplementary Figure 2, Supplementary Figure 3). While all these loci were recently discovered in a GWAS of 3.4 million individuals in the GSCAN study, here we reproduce some of the GSCAN findings with a considerably smaller sample size. Genome-wide significant (GWS) loci were defined as those with p<5.00E-08 with LD r2>0.1, within a 1MB window, based on the structure of the Haplotype Reference Consortium (HRC) multi-ancestry reference panel for the multi-ancestry meta-analysis, or the HRC ancestry-appropriate reference panel otherwise. To identify TUD risk loci and lead SNPs, we performed LD clumping in FUMA41 using a range of 3 Mb, r2 >0.1, and the respective ancestry 1000 Genome reference panel. Genomic risk loci that were located <1Mb apart were incorporated into a single locus. For loci that harbored multiple variants, we used conditional & joint association analysis using GWAS summary statistics (COJO) in Genome-wide Complex Trait Analysis (GCTA) software to define independent variants by conditioning them on the most significant variant within each locus. Following conditioning, significant variants (p<5.00E-08) were considered independent. From supplementary table 7.
Authors:
Sylvanus Toikumo, Mariela V Jennings, Benjamin K Pham, Hyunjoon Lee, Travis T Mallard, Sevim B Bianchi, John J Meredith, Laura Vilar-Ribó, Heng Xu, Alexander S Hatoum, Emma C Johnson, Vanessa K Pazdernik, Zeal Jinwala, Shreya R Pakala, Brittany S Leger, Maria Niarchou, Michael Ehinmowo, , Greg D Jenkins, Anthony Batzler, Richard Pendegraft, Abraham A Palmer, Hang Zhou, Joanna M Biernacka, Brandon J Coombes, Joel Gelernter, Ke Xu, Dana B Hancock, Nancy J Cox, Jordan W Smoller, Lea K Davis, Amy C Justice, Henry R Kranzler, Rachel L Kember, Sandra Sanchez-Roige
103 lead SNPs (83 independent loci) for the tobacco use disorder cross-ancestry meta-analysis, including the UK Biobank sample ("TUD-multi+UKBB"). The primary multi-ancestry meta-analysis of 20,801,211 imputed SNPs (lambda λGC=1.141, Figure 2) was performed on seven cohorts from four U.S. biobanks, comprising 653,790 individuals with TUD phecode data available, with 75.71% EUR, 17.50% AA, and 6.79% LA. We defined cases as patients who received at least two TUD ICD-9 or −10 codes (corresponding to the phecode definition) in their medical records, and controls as patients who had no TUD diagnosis codes. The summary statistics for TUD in UKBB were downloaded from the GWAS atlas (https://atlas.ctglab.nl/traitDB/3439). In UKBB only, cases were defined as having 1 ICD-10 code for TUD, and controls had none (10,287 cases and 234,603 controls). Genome-wide significant (GWS) loci were defined as those with p<5.00E-08 with LD r2>0.1, within a 1MB window, based on the structure of the Haplotype Reference Consortium (HRC) multi-ancestry reference panel for the multi-ancestry meta-analysis, or the HRC ancestry-appropriate reference panel otherwise. To identify TUD risk loci and lead SNPs, we performed LD clumping in FUMA41 using a range of 3 Mb, r2 >0.1, and the respective ancestry 1000 Genome reference panel. Genomic risk loci that were located <1Mb apart were incorporated into a single locus. For loci that harbored multiple variants, we used conditional & joint association analysis using GWAS summary statistics (COJO) in Genome-wide Complex Trait Analysis (GCTA) software to define independent variants by conditioning them on the most significant variant within each locus. Following conditioning, significant variants (p<5.00E-08) were considered independent. From supplementary table 8.
Authors:
Sylvanus Toikumo, Mariela V Jennings, Benjamin K Pham, Hyunjoon Lee, Travis T Mallard, Sevim B Bianchi, John J Meredith, Laura Vilar-Ribó, Heng Xu, Alexander S Hatoum, Emma C Johnson, Vanessa K Pazdernik, Zeal Jinwala, Shreya R Pakala, Brittany S Leger, Maria Niarchou, Michael Ehinmowo, , Greg D Jenkins, Anthony Batzler, Richard Pendegraft, Abraham A Palmer, Hang Zhou, Joanna M Biernacka, Brandon J Coombes, Joel Gelernter, Ke Xu, Dana B Hancock, Nancy J Cox, Jordan W Smoller, Lea K Davis, Amy C Justice, Henry R Kranzler, Rachel L Kember, Sandra Sanchez-Roige
Credible set analysis using FINEMAP in TUD-EUR analysis. We conducted independent GWAS of TUD cases and controls in individuals of European (EUR) ancestry across four PsycheMERGE sites (BioVU, MGBB, PMBB, and MVP) and performed a GWAS meta-analysis. We defined cases as patients who received at least two TUD ICD-9 or −10 codes (corresponding to the phecode definition) in their medical records, and controls as patients who had no TUD diagnosis codes. TUD-EUR included 11,422,241 imputed SNPs in a cohort of 163,734 TUD cases and 331,271 controls, which is 8.5 times larger than the total sample size of previous nicotine dependence GWAS. Genome-wide significant (GWS) loci were defined as those with p<5.00E-08 with LD r2>0.1, within a 1MB window, based on the structure of the Haplotype Reference Consortium (HRC) multi-ancestry reference panel for the multi-ancestry meta-analysis, or the HRC ancestry-appropriate reference panel otherwise. To identify TUD risk loci and lead SNPs, we performed linkage-disequilibrium (LD) clumping in FUMA using a range of 3 Mb, r2 >0.1, and the respective ancestry 1000 Genome reference panel. Genomic risk loci that were located <1Mb apart were incorporated into a single locus. For loci that harbored multiple variants, we used conditional & joint association analysis using GWAS summary statistics (COJO) in Genome-wide Complex Trait Analysis (GCTA) software to define independent variants by conditioning them on the most significant variant within each locus. Following conditioning, significant variants (p<5.00E-08) were considered independent. We determined credible variants among the independent variants by merging risk variants within 1Mb of the lead variant and fine-mapped the resulting region with 95% credible sets using FINEMAP. All loci from the credible set analysis are shown here. From supplementary table 11.
Authors:
Sylvanus Toikumo, Mariela V Jennings, Benjamin K Pham, Hyunjoon Lee, Travis T Mallard, Sevim B Bianchi, John J Meredith, Laura Vilar-Ribó, Heng Xu, Alexander S Hatoum, Emma C Johnson, Vanessa K Pazdernik, Zeal Jinwala, Shreya R Pakala, Brittany S Leger, Maria Niarchou, Michael Ehinmowo, , Greg D Jenkins, Anthony Batzler, Richard Pendegraft, Abraham A Palmer, Hang Zhou, Joanna M Biernacka, Brandon J Coombes, Joel Gelernter, Ke Xu, Dana B Hancock, Nancy J Cox, Jordan W Smoller, Lea K Davis, Amy C Justice, Henry R Kranzler, Rachel L Kember, Sandra Sanchez-Roige
Credible set analysis using FINEMAP in TUD-EUR analysis. We conducted independent GWAS of TUD cases and controls in individuals of European (EUR) ancestry across four PsycheMERGE sites (BioVU, MGBB, PMBB, and MVP) and performed a GWAS meta-analysis. We defined cases as patients who received at least two TUD ICD-9 or −10 codes (corresponding to the phecode definition) in their medical records, and controls as patients who had no TUD diagnosis codes. TUD-EUR included 11,422,241 imputed SNPs in a cohort of 163,734 TUD cases and 331,271 controls, which is 8.5 times larger than the total sample size of previous nicotine dependence GWAS. Genome-wide significant (GWS) loci were defined as those with p<5.00E-08 with LD r2>0.1, within a 1MB window, based on the structure of the Haplotype Reference Consortium (HRC) multi-ancestry reference panel for the multi-ancestry meta-analysis, or the HRC ancestry-appropriate reference panel otherwise. To identify TUD risk loci and lead SNPs, we performed linkage-disequilibrium (LD) clumping in FUMA using a range of 3 Mb, r2 >0.1, and the respective ancestry 1000 Genome reference panel. Genomic risk loci that were located <1Mb apart were incorporated into a single locus. For loci that harbored multiple variants, we used conditional & joint association analysis using GWAS summary statistics (COJO) in Genome-wide Complex Trait Analysis (GCTA) software to define independent variants by conditioning them on the most significant variant within each locus. Following conditioning, significant variants (p<5.00E-08) were considered independent. We determined credible variants among the independent variants by merging risk variants within 1Mb of the lead variant and fine-mapped the resulting region with 95% credible sets using FINEMAP. All loci from the credible set analysis are shown here. From supplementary table 11.
Authors:
Sylvanus Toikumo, Mariela V Jennings, Benjamin K Pham, Hyunjoon Lee, Travis T Mallard, Sevim B Bianchi, John J Meredith, Laura Vilar-Ribó, Heng Xu, Alexander S Hatoum, Emma C Johnson, Vanessa K Pazdernik, Zeal Jinwala, Shreya R Pakala, Brittany S Leger, Maria Niarchou, Michael Ehinmowo, , Greg D Jenkins, Anthony Batzler, Richard Pendegraft, Abraham A Palmer, Hang Zhou, Joanna M Biernacka, Brandon J Coombes, Joel Gelernter, Ke Xu, Dana B Hancock, Nancy J Cox, Jordan W Smoller, Lea K Davis, Amy C Justice, Henry R Kranzler, Rachel L Kember, Sandra Sanchez-Roige
Neocortex Gene Expression Correlates for AMDIST30 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMDIST30 measures Morphine distance (cm) travelled minutes 15-30 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMDIST45 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMDIST45 measures Morphine distance (cm) travelled minutes 30-45 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMDIST60 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMDIST60 measures Morphine distance (cm) travelled minutes 45-60 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMDIST75 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMDIST75 measures Morphine distance (cm) travelled minutes 60-75 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for NEPVCOUNT60 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The NEPVCOUNT60 measures Novel environment rears 45-60 min in the periphery under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Whole Brain Gene Expression Correlates for ST_PCT_PPI_70 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ST_PCT_PPI_70 measures Prepulse inhibition at 70db under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Whole Brain Gene Expression Correlates for ST_PCT_PPI_80 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ST_PCT_PPI_80 measures Prepulse inhibition at 80db under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Whole Brain Gene Expression Correlates for ST_PCT_STARTLE_70 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ST_PCT_STARTLE_70 measures Acoustic Startle Response Percentage of maximum startle response at 70 db under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Whole Brain Gene Expression Correlates for ST_PCT_STARTLE_80 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ST_PCT_STARTLE_80 measures Acoustic Startle Response Percentage of maximum startle response at 80 db under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for ADUL_RMS_BRDU measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The ADUL_RMS_BRDU measures Neurogenesis- BrdU labeled new neurons in Adult Rostral Migratory Stream 1 hr post BrdU under the domain Neurogenesis. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for ADUL_RMS_BRDU measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The ADUL_RMS_BRDU measures Neurogenesis- BrdU labeled new neurons in Adult Rostral Migratory Stream 1 hr post BrdU under the domain Neurogenesis. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMCNT30 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMCNT30 measures Morphine photocell counts minutes 15-30 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMCNT30 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMCNT30 measures Morphine photocell counts minutes 15-30 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMCNT30 measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMCNT30 measures Morphine photocell counts minutes 15-30 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMCNT45 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMCNT45 measures Morphine photocell counts minutes 30-45 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMCNT45 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMCNT45 measures Morphine photocell counts minutes 30-45 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for AMCNT45 measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMCNT45 measures Morphine photocell counts minutes 30-45 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
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