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Volume 139, Issue 5, Pages e6 (November 2010)

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1 Volume 139, Issue 5, Pages 1567-1576.e6 (November 2010)
Genome-Wide Association Study Identifies Variants Associated With Histologic Features of Nonalcoholic Fatty Liver Disease  Naga Chalasani, Xiuqing Guo, Rohit Loomba, Mark O. Goodarzi, Talin Haritunians, Soonil Kwon, Jinrui Cui, Kent D. Taylor, Laura Wilson, Oscar W. Cummings, Yii-Der Ida Chen, Jerome I. Rotter  Gastroenterology  Volume 139, Issue 5, Pages e6 (November 2010) DOI: /j.gastro Copyright © 2010 AGA Institute Terms and Conditions

2 Figure 1 (A) Manhattan Plot for NAS. X-axis is chromosome number, and y-axis is –log10(P value) from GWAS. Each point represents a profiled SNP. (B) Manhattan plot for fibrosis. X-axis is chromosome number, and y-axis is −log10(P value) from GWAS. Each point represents a profiled SNP. The arrow indicates the SNP with P < 1.0e-06. (C) Manhattan plot for lobular inflammation. X-axis is chromosome number, and y-axis is −log10(P value) from the GWAS. Each point represents a profiled SNP. The arrow indicates the SNP with P < 1.0e-06. Gastroenterology  , e6DOI: ( /j.gastro ) Copyright © 2010 AGA Institute Terms and Conditions

3 Figure 2 (A) Regional plot for NAS. The –log10(P value) from association analysis is shown for all SNPs in the region around the top SNP rs for NAS (50 kilobases on each side). X-axis shows position of the SNPs along chromosome 8; y-axis in the left gives –log10(P value). P values were obtained from association analysis when including age and BMI as covariates and assuming an additive genetic model. Y-axis in the right shows recombination rate (cM/Mb). The r2 shows measure of the linkage disequilibrium between this SNP and target SNP. The genes (NEIL2, FDFT1, and CTSB) are located in the region as indicated at the bottom portion of the figure. (B) Regional plot for fibrosis. The –log10(P value) from association analysis is shown for all SNPs in the region around the top SNP rs for fibrosis (50 kilobases on each side). X-axis shows position of the SNPs along chromosome 7; y-axis gives –log10(P value). P values were obtained from association analysis that included age, BMI, diabetic status, waist/hip ratio and HbA1c as covariates and assuming a recessive genetic model. Y-axis in the right shows recombination rate (cM/Mb). The r2 shows measure of the linkage disequilibrium between this SNP and target SNP. Gastroenterology  , e6DOI: ( /j.gastro ) Copyright © 2010 AGA Institute Terms and Conditions

4 Supplementary Figure 1 Cohort sample selection flowchart. Study subjects were those with histologically assessed nonalcoholic fatty liver disease (NAFLD) available for genotype-phenotype correlation. Gastroenterology  , e6DOI: ( /j.gastro ) Copyright © 2010 AGA Institute Terms and Conditions

5 Supplementary Figure 2 Regional plot for lobular inflammation. The –log10(P value) from association analysis is shown for all SNPs in the region around the top SNP rs for lobular inflammation (50 kilobases on each side). X-axis shows position of the SNPs along chromosome 10; y-axis gives –log10(P value). P values were obtained from association analysis when including age and BMI as covariates and assuming a recessive genetic model. Y-axis in the right shows recombination rate (cM/Mb). The r2 shows measure of the linkage disequilibrium between this SNP and the target SNP. The COL13A1 gene is located in the region as indicated at the bottom portion of the figure. Gastroenterology  , e6DOI: ( /j.gastro ) Copyright © 2010 AGA Institute Terms and Conditions

6 Supplementary Figure 3 Manhattan plots for aspartate aminotransferase (AST). X-axis is chromosome number, and y-axis is –log10(P value) from the GWAS. Each point represents a profiled SNP. Gastroenterology  , e6DOI: ( /j.gastro ) Copyright © 2010 AGA Institute Terms and Conditions

7 Supplementary Figure 4 Regional plot for aspartate aminotransferase (AST). The –log10(P value) from association analysis is shown for all SNPs in the region around the top SNP rs for AST (50 kilobases on each side). X-axis shows position of the SNPs along chromosome 12; y-axis gives –log10(P value). P values were obtained from association analysis when including age and BMI as covariates and assuming a dominant genetic model. Y-axis in the right shows recombination rate (cM/Mb). The r2 shows measure of the linkage disequilibrium between this SNP and target SNP. The PZP gene is located in the region as indicated at the bottom portion of the figure. Gastroenterology  , e6DOI: ( /j.gastro ) Copyright © 2010 AGA Institute Terms and Conditions

8 Supplementary Figure 5 (A) QQ plot for NAS. The –log10(P value) of observed association statistics is shown in y-axis, compared with–log10(P value) of the association statistics expected under the null hypothesis of no association in x-axis. Deviation from the expected P value is observed above –log10(Expected P value) of approximately 3.5. Genomic inflation factor (λ) is (B) QQ plot for fibrosis. The –log10(P value) of observed association statistics is shown in y-axis, compared with –log10(P value) of the association statistics expected under the null hypothesis of no association in x-axis. Deviation from the expected P value is observed above –log10(Expected P value) of approximately 3. Genomic inflation factor (λ) is (C) QQ plot for lobular inflammation. The –log10(P value) of observed association statistics is shown in y-axis, compared with–log10(P value) of the association statistics expected under the null hypothesis of no association in x-axis. Deviation from the expected P value is observed above –log10(Expected P value) of approximately 4. Genomic inflation factor (λ) is (D) QQ plot for AST. The –log10(P value) of observed association statistics is shown in y-axis, compared with –log10(P value) of the association statistics expected under the null hypothesis of no association in x-axis. Deviation from the expected P value is observed above –log10(Expected P value) of approximately 3.5. Genomic inflation factor (λ) is Gastroenterology  , e6DOI: ( /j.gastro ) Copyright © 2010 AGA Institute Terms and Conditions

9 Supplementary Figure 5 (A) QQ plot for NAS. The –log10(P value) of observed association statistics is shown in y-axis, compared with–log10(P value) of the association statistics expected under the null hypothesis of no association in x-axis. Deviation from the expected P value is observed above –log10(Expected P value) of approximately 3.5. Genomic inflation factor (λ) is (B) QQ plot for fibrosis. The –log10(P value) of observed association statistics is shown in y-axis, compared with –log10(P value) of the association statistics expected under the null hypothesis of no association in x-axis. Deviation from the expected P value is observed above –log10(Expected P value) of approximately 3. Genomic inflation factor (λ) is (C) QQ plot for lobular inflammation. The –log10(P value) of observed association statistics is shown in y-axis, compared with–log10(P value) of the association statistics expected under the null hypothesis of no association in x-axis. Deviation from the expected P value is observed above –log10(Expected P value) of approximately 4. Genomic inflation factor (λ) is (D) QQ plot for AST. The –log10(P value) of observed association statistics is shown in y-axis, compared with –log10(P value) of the association statistics expected under the null hypothesis of no association in x-axis. Deviation from the expected P value is observed above –log10(Expected P value) of approximately 3.5. Genomic inflation factor (λ) is Gastroenterology  , e6DOI: ( /j.gastro ) Copyright © 2010 AGA Institute Terms and Conditions


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