Michael J. Bray, B. S. , Todd L. Edwards, Ph. D. , Melissa F

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Presentation transcript:

Admixture mapping of uterine fibroid size and number in African American women  Michael J. Bray, B.S., Todd L. Edwards, Ph.D., Melissa F. Wellons, M.D., Sarah H. Jones, B.A., Katherine E. Hartmann, M.D., Ph.D., Digna R. Velez Edwards, Ph.D.  Fertility and Sterility  Volume 108, Issue 6, Pages 1034-1042.e26 (December 2017) DOI: 10.1016/j.fertnstert.2017.09.018 Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Admixture mapping analysis of chromosome 10 with overlapping single nucleotide polymorphism (SNP) association analysis results. The X-axis indicates the genomic position along chromosome 10 in Mb. The top of the Y-axis indicates -log10(P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs12219990; dashed green line = conditioned on rs12219990) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, body mass index (BMI), five principal components. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 56,258,202 to 59,854,651 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs12219990, was imputed (BioVU info score, 0.921; CARDIA info score, 0.922). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 Quality control flow chart of Coronary Artery Risk Development in Young Adults Study (CARDIA) African American participants. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 2 Quality control flow chart of biorepository at Vanderbilt University (BioVU) African American participants. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 3 Graph of the principal component analysis of Coronary Artery Risk Development in Young Adults Study (CARDIA) African American participants plotted with individuals from the 1,000 Genomes Project. AMR =Ad Mixed American; EAS = East Asian; EUR = European; SAS = South Asian; ACB = African Caribbean in Barbados; ASW = Americans of African Ancestry in SW USA; AFR = African. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 4 Graph of the principal component analysis of biorepository at Vanderbilt University (BioVU) African American participants plotted with individuals from the 1,000 Genomes Project. AMR =Ad Mixed American; EAS = East Asian; EUR = European; SAS = South Asian; ACB = African Caribbean in Barbados; ASW = Americans of African Ancestry in SW USA; AFR = African. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 5 The QQ plot for the meta-analysis of the admixture mapping results for fibroid number (single vs. multiple) between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 6 The QQ plot for the admixture mapping results for fibroid number (single vs. multiple) for biorepository at Vanderbilt University (BioVU) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 7 The QQ plot for the admixture mapping results for fibroid number (single vs. multiple) for Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 8 The QQ plot for the meta-analysis of the admixture mapping results for log10 transformed volume of largest fibroid between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 9 The QQ plot for the admixture mapping results for log10 transformed volume of largest fibroid for biorepository at Vanderbilt University (BioVU) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 10 The QQ plot for the admixture mapping results for log10 transformed volume of largest fibroid for Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 11 The QQ plot for the meta-analysis of the admixture mapping results for log10 transformed largest dimension of all fibroids between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 12 The QQ plot for the admixture mapping results for log10 transformed largest dimension of all fibroids for biorepository at Vanderbilt University (BioVU) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 13 The QQ plot for the admixture mapping results for log10 transformed largest dimension of all fibroids for Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs). The regression analyses were adjusted for age, body mass index (BMI), five principal components. Markers with a minor allele frequency of at least 5% were used in the admixture mapping analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 14 Admixture mapping analysis of chromosome 10 with overlapping single nucleotide polymorphism (SNP) association analysis results with and without adjustment for body mass index (BMI). The X-axis indicates the genomic position along chromosome 10 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs12219990; dashed green line = conditioned on rs12219990) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, BMI, five principal components. The solid orange line represents the admixture mapping analysis that was adjusted for age and five principal components only. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 56,258,202 to 59,854,651 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs12219990, was imputed (BioVU info score, 0.921; CARDIA info score, 0.922). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 15 Admixture mapping analysis of chromosome 14 with overlapping single nucleotide polymorphism (SNP) association analysis results with and without adjustment for body mass index (BMI). The X-axis indicates the genomic position along chromosome 14 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs11394508; dashed green line = conditioned on rs11394508) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, BMI, five principal components. The solid orange line represents the admixture mapping analysis that was adjusted for age and five principal components only. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 72,802,666 to 79,205,619 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs11394508, was imputed (BioVU info score, 0.995; CARDIA info score, 0.956). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 16 Admixture mapping analysis of chromosome 2 with overlapping single nucleotide polymorphism (SNP) association analysis results with and without adjustment for body mass index (BMI). The X-axis indicates the genomic position along chromosome 2 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs6723563; dashed green line = conditioned on rs6723563) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, BMI, five principal components. The solid orange line represents the admixture mapping analysis that was adjusted for age and five principal components only. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 123,221,985 to 131,110,097 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs6723563, was imputed (BioVU info score, 0.932; CARDIA info score, 0.885). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 17 Admixture mapping analysis of chromosome 7 with overlapping single nucleotide polymorphism (SNP) association analysis results with and without adjustment for body mass index (BMI). The X-axis indicates the genomic position along chromosome 7 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs782525; dashed green line = conditioned on rs7872525) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, BMI, five principal components. The solid orange line represents the admixture mapping analysis that was adjusted for age and five principal components only. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 129,822,797 to 134,670,462 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs782525, was imputed (BioVU info score, 0.999; CARDIA info score, 0.985). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 18 Admixture mapping analysis of chromosome 3 with overlapping single nucleotide polymorphism (SNP) association analysis results with and without adjustment for body mass index (BMI). The X-axis indicates the genomic position along chromosome 3 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs112428319; dashed green line = conditioned on rs112428319) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, BMI, five principal components. The solid orange line represents the admixture mapping analysis that was adjusted for age and five principal components only. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 63,405,151 to 66,558,036 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs112428319, was imputed (BioVU info score, 0.9998; CARDIA info score, 0.994). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 19 Admixture mapping analysis of chromosome 10 with overlapping single nucleotide polymorphism (SNP) association analysis results with and without adjustment for body mass index (BMI). The X-axis indicates the genomic position along chromosome 10 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs4919512; dashed green line = conditioned on rs4919512) with fibroid volume (log10 transformed) as the outcome. The admixture mapping analysis was adjusted for age, BMI, five principal components. The solid orange line represents the admixture mapping analysis that was adjusted for age and five principal components only. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid volume (log10 transformed) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 98,747,114 to 103,009,908 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs4919512, was genotyped for BioVU but imputed for CARDIA (BioVU info score, 1; CARDIA info score, 0.801). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 20 Admixture mapping analysis of chromosome 12 with overlapping single nucleotide polymorphism (SNP) association analysis results with and without adjustment for body mass index (BMI). The X-axis indicates the genomic position along chromosome 10 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs2575289 or rs56133667; dashed teal line = conditioned on rs2575289; dashed yellow line = conditioned on rs56133667; dashed purple line = conditioned on rs2575289 and rs56133667) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, BMI, five principal components. The solid orange line represents the admixture mapping analysis that was adjusted for age and five principal components only. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 61,300,873 to 67,610,913 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs2575289, was imputed (BioVU info score, 0.976; CARDIA info score, 0.991). The SNP, rs56133667, was imputed (BioVU info score, >0.999; CARDIA info score, >0.999). The dotted red line represents the significance threshold of the single SNP association analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 21 Admixture mapping analysis of chromosome 10 with overlapping single nucleotide polymorphism (SNP) association analysis results. The X-axis indicates the genomic position along chromosome 10 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs4919512; dashed green line = conditioned on rs4919512) with fibroid volume (log10 transformed) as the outcome. The admixture mapping analysis was adjusted for age, body mass index (BMI), five principal components. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid volume (log10 transformed) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 98,747,114 to 103,009,908 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs4919512, was genotyped for BioVU but imputed for CARDIA (BioVU info score, 1; CARDIA info score, 0.801). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 22 Admixture mapping analysis of chromosome 14 with overlapping single nucleotide polymorphism (SNP) association analysis results. The X-axis indicates the genomic position along chromosome 14 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) AAs from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs11394508; dashed green line = conditioned on rs11394508) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, body mass index (BMI), five principal components. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 72,802,666 to 79,205,619 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs11394508, was imputed (BioVU info score, 0.995; CARDIA info score, 0.956). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 23 Admixture mapping analysis of chromosome 2 with overlapping single nucleotide polymorphism (SNP) association analysis results. The X-axis indicates the genomic position along chromosome 2 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs6723563; dashed green line = conditioned on rs6723563) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, body mass index (BMI), five principal components. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 123,221,985 to 131,110,097 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs6723563, was imputed (BioVU info score, 0.932; CARDIA info score, 0.885). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 24 Admixture mapping analysis of chromosome 3 with overlapping single nucleotide polymorphism (SNP) association analysis results. The X-axis indicates the genomic position along chromosome 3 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs112428319; dashed green line = conditioned on rs112428319) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, body mass index (BMI), five principal components. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 63,405,151 to 66,558,036 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs112428319, was imputed (BioVU info score, 0.9998; CARDIA info score, 0.994). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 25 Admixture mapping analysis of chromosome 7 with overlapping single nucleotide polymorphism (SNP) association analysis results. The X-axis indicates the genomic position along chromosome 7 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs782525; dashed green line = conditioned on rs7872525) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, body mass index (BMI), five principal components. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 129,822,797 to 134,670,462 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs782525, was imputed (BioVU info score, 0.999; CARDIA info score, 0.985). The dotted red line represents the significance threshold. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 26 Admixture mapping analysis of chromosome 12 with overlapping single nucleotide polymorphism (SNP) association analysis results. The X-axis indicates the genomic position along chromosome 10 in Mb. The top of the Y-axis indicates -log10 (P value) from the meta-analysis between biorepository at Vanderbilt University (BioVU) and Coronary Artery Risk Development in Young Adults Study (CARDIA) African Americans (AAs) from logistic regression of admixture mapping values that were generated from LAMP-ANC (solid black line = not conditioned for rs2575289 or rs56133667; dashed teal line = conditioned on rs2575289; dashed yellow line = conditioned on rs56133667; dashed purple line = conditioned on rs2575289 and rs56133667) with fibroid number (single vs. multiple) as the outcome. The admixture mapping analysis was adjusted for age, body mass index (BMI), five principal components. The solid green line represents the significance threshold. The solid blue line represents the suggestive threshold. The bottom portion of the Y-axis indicates the log10 (P value) for the single SNP association analyses (blue circles = genotyped SNPs; red circles = imputed SNPs) with fibroid number (single vs. multiple) as the outcome. The imputed region was found by taking 1 –log down from the most significant mapping peak above the suggest threshold. The imputed region encompassed 61,300,873 to 67,610,913 bp. The single SNP association analysis was adjusted for age, BMI, and five principal components. The SNP, rs2575289, was imputed (BioVU info score, 0.976; CARDIA info score, 0.991). The SNP, rs56133667, was imputed (BioVU info score, >0.999; CARDIA info score, >0.999). The dotted red line represents the significance threshold of the single SNP association analysis. Fertility and Sterility 2017 108, 1034-1042.e26DOI: (10.1016/j.fertnstert.2017.09.018) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions