ONLINE Supplemental Digital Material for

Relationship between Hypertension and Admixture in Post-Menopausal African

American and Hispanic American Women

Roman Kosoy, Lihong Qi, Rami Nassir, Lorena Garcia, Matthew Allison, Russell

Shigeta, John Robbins, and Michael F Seldin Table S1. Ancestry Informative Markers

NCBI Assembly Location Build on NCBI Allele Allele name Chr Number Assembly Strand 1 2 EURa AFR AMI rs10007810 4 36 41249121 Reverse A G 0.25 0.96 0.15 rs1040045 6 36 4692158 Forward A G 0.73 0.1 0.98 rs1040404 1 36 166426514 Reverse A G 0.24 0.9 0.88 rs10496971 2 36 145486413 Forward G T 0.09 0.06 0.49 rs10510228 3 36 2183832 Forward A G 0.92 0.9 0.37 rs10513300 9 36 119170027 Reverse C T 0.07 0 0.63 rs10839880 11 36 7806892 Forward C T 0.33 0.96 0.29 rs10954737 7 36 83370983 Reverse C T 0.08 0.04 0.51 rs11227699 11 36 66655068 Forward A G 0.1 0.58 0.63 rs11652805 17 36 60417613 Reverse C T 0.14 0.98 0.13 rs12130799 1 36 55435960 Forward A G 0.93 1 0.49 rs12439433 15 36 34007327 Reverse A G 0.94 0.99 0.44 rs12544346 8 36 86611868 Forward A G 0.6 0.02 0.28 rs12629908 3 36 122005406 Reverse A G 0.05 0.16 0.82 rs1296819 22 36 16456546 Forward A C 0.22 0.85 0.21 rs1325502 1 36 42132857 Forward A G 0.13 0.79 0.06 rs13400937 2 36 79718431 Forward G T 0.21 0.91 0.23 rs1369093 4 36 73464055 Reverse C T 0.05 0.33 0.72 rs1407434 1 36 184415655 Forward A G 0.12 0.29 0.85 rs1408801 9 36 12662320 Reverse A G 0.94 0.46 0.16 rs1471939 8 36 28997224 Reverse C T 0.17 0.32 0.93 rs1513181 3 36 190057690 Reverse A G 0.14 0.21 0.81 rs1760921 14 36 19887971 Reverse C T 0.04 0.8 0.28 rs1837606 11 36 15794713 Reverse C T 0.3 0.72 0.85 rs1871428 6 36 168408609 Reverse A G 0.4 0.98 0.72 rs1950993 14 36 57308440 Forward G T 0.63 0.02 0.28 rs200354 14 36 98445074 Forward G T 0.83 0.32 0.13 rs2030763 3 36 181447421 Reverse A G 0.15 0.03 0.7 rs2070586 12 36 107801849 Reverse A G 0.15 0.45 0.8 rs2073821 9 36 134922943 Forward C T 0.89 1 0.43 rs214678 12 36 45963217 Reverse C T 0.15 0.07 0.64 rs2306040 9 36 92681020 Reverse C T 0.08 0.06 0.67 rs2330442 7 36 42346596 Forward A G 0.59 0.05 0.26 rs2357442 14 36 51677717 Reverse A C 0.87 0.76 0.27 rs2416791 12 36 11592755 Forward A G 0.08 0.94 0.55 rs2504853 6 36 12643097 Reverse C T 0.35 0.97 0.58 rs260690 2 36 108946170 Forward A C 0.91 0.36 0.03 rs2627037 2 36 179314783 Forward A G 0.1 0.48 0.72 rs2702414 4 36 179636517 Reverse A G 0.06 0.1 0.71 rs2835370 21 36 36807495 Reverse C T 0.06 0.48 0.76 rs2899826 15 36 72521553 Forward A G 0.9 0.59 0.19 rs2946788 11 36 23967106 Reverse G T 0.26 0.92 0.13 rs2986742 1 36 6472963 Forward C T 0.1 0.77 0.1 rs3118378 1 36 68622275 Reverse A G 0.63 0.57 0.05 rs316598 5 36 2417626 Reverse C T 0.27 0.99 0.43 rs316873 1 36 240409127 Reverse C T 0.86 0.91 0.33 rs32314 7 36 32145649 Reverse C T 0.27 0.36 0.92 rs3737576 1 36 101482151 Reverse C T 0.05 0.02 0.75 rs3784230 14 36 104750100 Forward A G 0.58 0 0.47 rs3907047 20 36 53434321 Forward C T 0.06 0 0.63 rs3943253 8 36 13403871 Reverse A G 0.93 0.7 0.14 rs4463276 6 36 145097024 Forward A G 0.23 0.86 0.98 rs4666200 2 36 29391915 Forward A G 0.75 0.11 0.92 rs4670767 2 36 37794900 Forward G T 0.9 0.98 0.34 rs4717865 7 36 73092135 Reverse A G 0.11 0 0.64 rs4746136 10 36 74971000 Forward A G 0.13 0 0.78 rs4781011 16 36 10882812 Forward G T 0.77 0.4 0.06 rs4798812 18 36 9410504 Forward A G 0.23 0.27 0.8 rs4821004 22 36 30696359 Forward C T 0.6 0.06 0.61 rs4891825 18 36 66018643 Forward A G 0.89 0.09 0.9 rs4908343 1 36 27804285 Reverse A G 0.82 0.04 0.95 rs4918842 10 36 115306802 Reverse C T 0.15 0.09 0.93 rs4951629 1 36 210853506 Reverse C T 0.04 0.16 0.64 rs4984913 16 36 680467 Forward A G 0.75 0.07 0.29 rs5768007 22 36 46586536 Reverse C T 0.89 1 0.28 rs6104567 20 36 10143433 Reverse G T 0.31 0.09 0.88 rs6451722 5 36 43747135 Forward A G 0.24 0.9 0.01 rs647325 1 36 18043473 Reverse A G 0.8 0.39 0.06 rs6548616 3 36 79482265 Reverse C T 0.25 0.96 0.05 rs705308 7 36 97533299 Reverse A C 0.44 0.97 0.96 rs7238445 18 36 48035542 Forward A G 0.19 0.92 0.29 rs731257 7 36 12635776 Forward A G 0.09 0.02 0.81 rs734873 3 36 149233045 Forward A G 0.09 0.03 0.56 rs735480 15 36 42939663 Reverse C T 0.05 1 0.69 rs7421394 2 36 14673800 Reverse A G 0.67 0.04 0.28 rs7554936 1 36 149389113 Reverse C T 0.34 0.99 0.12 rs7657799 4 36 105594872 Forward G T 0.05 0.86 0.01 rs7745461 6 36 22019595 Forward A G 0.15 0.34 0.76 rs7803075 7 36 130392606 Reverse A G 0.29 1 0.9 rs7844723 8 36 122977684 Reverse C T 0.43 1 0.72 rs798443 2 36 7885726 Forward A G 0.83 0.03 0.68 rs7997709 13 36 33745737 Reverse C T 0.06 0.23 0.84 rs8035124 15 36 89906712 Reverse A C 0.84 0.22 0.14 rs8113143 19 36 38344087 Reverse A C 0.32 1 0.71 rs818386 16 36 63964209 Reverse C T 0.81 1 0.33 rs870347 5 36 6898035 Reverse A C 0.95 0.95 0.19 rs874299 18 36 73185272 Reverse C T 0.71 0.04 0.11 rs948028 11 36 120149657 Reverse A C 0.87 0.19 0.54 rs9522149 13 36 110625168 Reverse C T 0.76 0.03 0.06 rs9530435 13 36 74891888 Reverse C T 0.79 0.07 0.95 rs9809104 3 36 39121433 Reverse C T 0.19 0.92 0.15 rs9845457 3 36 137397166 Reverse A G 0.63 0.03 0.86 a. Frequency of allele 1. Table S2. Effect of Admixture on Hypertension in African American and Hispanic American WHI Participants: Supplemental Analyses

Adjusting for Years since Menopause

Entry Diastolic BP Entry Systolic BP Groupa Parameterb Estimatec SEd p-value Estimatec SEd p-value ALL AFR (age, BMI, MEN, SES) 0.53 0.03 <.0001 0.46 0.03 <.0001 AMI (age, BMI, MEN, SES) -0.99 0.06 <.0001 -0.76 0.06 <.0001 EUR (age, BMI, MEN, SES) -0.53 0.04 <.0001 -0.52 0.04 <.0001

AFA AFR (age, BMI, MEN, SES) 0.31 0.08 0.0002 0.38 0.08 <.0001

HA AFR (age, BMI, MEM, SES) 0.80 0.13 <.0001 0.67 0.13 <.0001 AMI (age, BMI, MEM, SES) -0.55 0.09 <.0001 -0.29 0.08 0.001 EUR (age, BMI, MEM, SES) 0.19 0.09 0.03 -0.01 0.08 0.90 a. The subject groups included all self-identified African Americans and Hispanic Americans (ALL- 12,587 subjects), self-identified AFA subjects with >0.2 AFR admixture, < 0.05 AMI (AFA -8202 subjects), and self-identified Hispanic Americans (HA – 3710 subjects). b. Analysis were performed with the covariates as noted estimating the effect of different continental admixture [sub-Saharan African, (AFR),

Amerindian (AMI) or European (EUR)]. The covariates were age (and age squared); years since menopause (MEN) body mass index (BMI), years since menopause and socioeconomic status (SES). c. The estimates are measured as the fraction of the standard deviation attributed to a unit increase in admixture. d. Standard error (SE) of the estimate is shown. Table S3. Admixture Risk for Hypertension: Supplemental Analysis Using Median BP from Multiple Vistisa

Odds Population Groupb Classificationc Normod Hyperd Admixturee 95% CIg p-value Ratiof ALL Diastolic 7691 3889 AFR 2.58 2.25 - 2.94 <.0001 Systolic 6794 5199 AFR 2.53 2.23 - 2.87 <.0001 Either 4482 4958 AFR 3.14 2.73 - 3.62 <.0001 Diastolic 7691 3889 AMI 0.18 0.13 - 0.24 <.0001 Systolic 6794 5199 AMI 0.21 0.16 - 0.28 <.0001 Either 4482 4958 AMI 0.15 0.11 - 0.20 <.0001 Diastolic 7691 3889 EUR 0.35 0.29 - 0.42 <.0001 Systolic 6794 5199 EUR 0.35 0.29 - 0.41 <.0001 Either 4482 4958 EUR 0.28 0.23 - 0.33 <.0001

AFA Diastolic 4562 2882 AFR 1.76 1.22 - 2.54 0.003 Systolic 3935 3805 AFR 1.84 1.29 - 2.64 0.001 Either 2442 3634 AFR 2.42 1.61 - 3.65 <.0001

HA Diastolic 2769 771 AFR 2.37 1.25 - 4.51 0.01 Systolic 2556 1076 AFR 2.01 1.10 - 3.65 0.02 Either 1846 1024 AFR 2.88 1.48 - 5.58 0.002 Diastolic 2769 771 AMI 0.51 0.32 - 0.81 0.004 Systolic 2556 1076 AMI 0.68 0.45 - 1.03 0.07 Either 1846 1024 AMI 0.55 0.35 - 0.86 0.01 Diastolic 2769 771 EUR 1.30 0.83 - 2.04 0.25 Systolic 2556 1076 EUR 1.07 0.71 - 1.61 0.75 Either 1846 1024 EUR 1.12 0.72 - 1.75 0.62

a. The median BP from two or more visits was used for this analysis. If there were an even number of BP recordings the lower of the two BP

recordings was used. b. The subject groups included all self-identified African Americans and Hispanic Americans (ALL), self-identified AFA subjects with >0.2

AFR admixture, < 0.05 AMI (AFA), and self-identified Hispanic Americans (HA). c. Number of individuals with all required phenotypic and covariate information. This number included the AFA and HA groups and additional

subjects that were self-identified AFA but did not meet our AFA subset definition (see Methods). The classification for each analysis was

as follows: Diastolic normotensive participants (Normo) were classified based on diastolic blood pressure < 80 mm Hg on no treatment

regimen. Systolic normotensive participants were classified based on systolic blood pressure < 130 mm Hg on no treatment regimen.

Diastolic hypertensive (Hyper) participants were either on treatment or with mean diastolic blood pressure > 90 mm Hg. Systolic

hypertensive participants were either on treatment or had mean systolic blood pressure >140 mm Hg. Individuals classified as "Either"

normotensive met both definitions for normotensive. Individuals classified as "Either" hypertensive met either or both criterion/criteria. d. The number of subjects meeting either normotensive (Normo) or hypertenisive (Hyper) for classification groups are indicated. These differ

from the total subject numbers in Table 1 due to the exclusion of individuals with intermediate BPs (80 – 90 mm Hg for diastolic or 130 –

140 mm Hg systolic with no treatment). We also note that individuals in the either category may have been classified as normotensive or

excluded (intermediate zone) for either diastolic or systolic definitions. e. The effect of admixture from sub-Saharan Africa (AFR), Amerindian (AMI) or European (EUR). f. The odds ratio (OR) attributed to a unit increase in admixture. For these analyses the OR reflects the propensity for hypertension

attributed to admixture of the indicated continental group. All analyses were performed using the following covariates determined from the

same clinic visit as median BP measurement: age, age squared, body mass index, and socioeconomic status. g. 95% confidence interval for OR. Table S4. Effect of Admixture on Pulse Pressure in African American and Hispanic American WHI Participants Pulse Pressure Group Parametera Estimateb SE p-value ALL AFR 0.37 0.02 <.0001 AFR (age and BMI) 0.26 0.02 <.0001 AFR (age, BMI, SES) 0.24 0.02 <.0001

AMI -0.59 0.05 <.0001 AMI (age and BMI) -0.31 0.05 <.0001 AMI (age, BMI, SES) -0.32 0.05 <.0001

EUR -0.43 0.03 <.0001 EUR (age and BMI) -0.34 0.03 <.0001 EUR (age, BMI, SES) -0.30 0.03 <.0001

AFA AFR 0.17 0.07 0.02 AFR (age and BMI) 0.30 0.07 <.0001 AFR (age, BMI, SES) 0.23 0.07 0.001

HISP AFR 0.37 0.12 0.002 AFR (age and BMI) 0.28 0.11 0.008 AFR (age, BMI, SES) 0.25 0.11 0.02

EUR -0.09 0.08 0.23 EUR (age and BMI) -0.20 0.07 0.003 EUR (age, BMI, SES) -0.15 0.07 0.04

AMI -0.07 0.08 0.39 AMI (age and BMI) 0.09 0.07 0.23 AMI (age, BMI, SES) 0.04 0.07 0.57 a. Analysis was performed with covariates including age (and age squared), body mass index (BMI) and socioeconomic status (SES). b. The estimates are measured as the fraction of the standard deviation attributed to a unit increase in admixture. Supplemental Acknowledgements

We thank the following institutes, centers and investigators of the Women’s Health Initiative (WHI) who developed and implemented the recruitment of participants, and the clinical and laboratory studies for WHI. Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles Kooperberg; (Medical Research Labs, Highland Heights, KY) Evan Stein; (University of California at San Francisco, San Francisco, CA) Steven Cummings. Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX) Haleh Sangi- Haghpeykar; (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (Brown University, Providence, RI) Charles B. Eaton; (Emory University, Atlanta, GA) Lawrence S. Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA) Shirley Beresford; (George Washington University Medical Center, Washington, DC) Lisa Martin; (Los Angeles Biomedical Research Institute at Harbor- UCLA Medical Center, Torrance, CA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR) Erin LeBlanc; (Kaiser Permanente Division of Research, Oakland, CA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Northwestern University, Chicago/Evanston, IL) Linda Van Horn; (Rush Medical Center, Chicago, IL) Henry Black; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (State University of New York at Stony Brook, Stony Brook, NY) Dorothy Lane; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL) Cora E. Lewis; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA) John Robbins; (University of California at Irvine, CA) F. Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA) Lauren Nathan; (University of California at San Diego, LaJolla/Chula Vista, CA) Robert D. Langer; (University of Cincinnati, Cincinnati, OH) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Hawaii, Honolulu, HI) J. David Curb; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ) Norman Lasser; (University of Miami, Miami, FL) Mary Jo O’Sullivan; (University of Minnesota, Minneapolis, MN) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (University of Tennessee Health Science Center, Memphis, TN) Karen C. Johnson; (University of Texas Health Science Center, San Antonio, TX) Robert Brzyski; (University of Wisconsin, Madison, WI) Gloria E. Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC) Mara Vitolins; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI) Michael S. Simon.. Women’s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker.