SUPPLEMENTARY DATA Principal Investigators and Acknowledgment
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SUPPLEMENTARY DATA Principal Investigators and Acknowledgment Hispanic Community Health Study/Study of Latinos (HSHC/SOL) Robert Kaplan, Sylvia Wassertheil-Smoller (Bronx); Martha L. Daviglus, Aida L. Giachello (Chicago); Neil Schneiderman, David Lee, Leopoldo Raij, John Ryan (Miami); Greg Talavera, John Elder, Matthew Allison, Michael Criqui (San Deigo). The authors thank the staff and participants of HCHS/SOL for their important contributions. A complete list of staff and investigators has been provided by Sorlie P., et al. in Ann Epidemiol. 2010 ;20:642-649 and is also available on the study website http://www.cscc.unc.edu/hchs/. The baseline examination of the Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contributed to the HCHS/SOL first funding period through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the NIH Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000123, and NIDDK Diabetes Research Center (DRC) grant DK063491. Starr County Health Study (SCHS) We thank the field staff in Starr County for their collection of these data and are grateful to the study participants who gave of their time and contributed to this study. This work was supported in part by grants DK073541, DK020595, AI085014, DK085501, and HL102830 from the National Institutes of Health and funds from the University of Texas Health Science Center at Houston. These studies (protocol SPH-02-042) were approved by the University of Texas Health Science Center at Houston’s Committee for the Protection of Human Subjects and carried out in a manner consistent with the Declaration of Helsinki. The studies were explained to all participants and written informed consent obtained. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the National Institutes of Health (NIH) to The Johns Hopkins University, contract number HHSN268200782096C. Boston Puerto Rican Health Study (BPRHS) Katherine Tucker. The Boston Puerto Rican Health Study was funded by National Heart, Lung, and Blood Institute grant P50-HL105185 and National Institute on Aging grant P01-AG023394. BioMe Biobank Judy H Cho. We thank the participants in the BioMe Biobank for their invaluable contribution to biomedical research. Funding for the BioMe Biobank program is supported by the Andrea and Charles Bronfman Philanthropies. ©2019 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc19-0168/-/DC1 SUPPLEMENTARY DATA Supplementary Table S1. Characteristics of study samples without diabetes HCHS/SOL SCHS BPRHS BioMe-OMNIBioMe-MEGA No. of participants, n All 9636 395 832 1867 1683 men 4040 89 245 640 564 women 5596 306 587 1227 1119 Age, years 43.8 (13.8) 48.13 (8.68) 56.0 (NA) 50.2 (14.7) 51.3 (14.8) HbA1c, % 5.47 (0.36) 5.45 (0.35) 6.09 (NA) 5.55 (0.41) 5.56 (0.42) Hispanic background, n Central American 1097 0 0 76 50 Cuban 1750 0 0 25 17 Dominican 904 0 0 244 278 Mexican 3558 395 0 35 42 Puerto Rican 1533 0 831 488 404 South American 765 0 0 152 204 Data are mean (SD) or sample size (n). ©2019 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc19-0168/-/DC1 SUPPLEMENTARY DATA Supplementary Table S2. Associations of 18 newly identified SNPs with HbA1c levels (%) in the HCHS/SOL (P<1×10-5) and in replication studies Allele HCHS/SOL Replication studies* Combined P SNP Nearest locus Chr Position Effect Other EAF Beta (SE) P Beta (SE) P (SOL+ replication)† rs113282222b CEP104 1 3718591 TGGAG T 0.173 -0.031 (0.006) 9.98E-07 -0.006 (0.012) 0.595 5.94E-06 rs199584848b TM1EM206 1 212544641 A AAG 0.024 0.080 (0.015) 1.74E-07 0.006 (0.102) 0.953 2.27E-07 rs113119484a CADM2 3 85463419 T G 0.013 -0.102 (0.021) 8.86E-07 0.016 (0.034) 0.642 7.42E-05 rs10513537b IQCJ−SCHIP1 3 158904859 G A 0.209 0.031 (0.006) 3.83E-07 0.003 (0.012) 0.778 3.07E-06 rs74638476b ETV5 3 185735512 T C 0.026 0.079 (0.016) 8.03E-07 -0.005 (0.029) 0.872 2.32E-05 rs73774950a NUDT12 5 102957617 C T 0.024 -0.089 (0.016) 3.09E-08 0.016 (0.024) 0.513 2.19E-05 rs11752643a HLA−DQA2 6 32669373 T C 0.017 0.096 (0.018) 1.76E-07 0.012 (0.035) 0.737 1.77E-06 rs6949071b ETV1 7 13655049 C G 0.459 -0.025 (0.005) 4.50E-07 0.005 (0.010) 0.646 1.70E-05 rs6992753b UNC5D 8 35926402 A G 0.016 0.111 (0.020) 3.48E-08 0.017 (0.030) 0.581 9.51E-07 rs116781682b FAM188A 10 16218532 T C 0.012 -0.118 (0.023) 2.11E-07 -0.050 (0.035) 0.156 2.82E-07 rs334b HBB 11 5248232 A T 0.013 -0.305 (0.023) 2.72E-40 -0.127 (0.044) 0.004 2.94E-39 rs73393695a FBXO21 12 117644934 A G 0.051 -0.056 (0.011) 6.38E-07 -0.001 (0.020) 0.975 1.21E-05 rs145546625b HBM 16 220583 T C 0.066 0.059 (0.010) 8.20E-09 0.044 (0.023) 0.050 1.42E-09 rs144212976b RAB11FIP4 17 29821839 G A 0.020 0.087 (0.017) 5.51E-07 -0.013 (0.037) 0.719 1.24E-05 rs2748424b TMC6 17 76124865 G C 0.179 0.051 (0.006) 1.98E-15 0.032 (0.012) 0.008 1.49E-16 rs74575505b SIGLEC12 19 51942103 G A 0.128 0.036 (0.007) 7.27E-07 -0.007 (0.014) 0.622 2.67E-05 rs56222990b PDGFB 22 39652947 G C 0.069 0.045 (0.010) 6.34E-06 0.012 (0.017) 0.482 1.36E-04 rs1050828a G6PD X 153764217 T C 0.020 -0.346 (0.014) 9.59E-132 -0.292 (0.099) 0.003 1.34E-133 Chr, chromosome; Position: GRCh37 reference; EAF: effect allele frequency; Beta: effect size (%) for each effect allele of SNP on HbA1c. *Results from 4 replication studies (see Supplemental Table 3) were combined by fixed effect meta-analysis. †Results from SOL and replication studies were combined using by fixed effect meta-analysis. a genotyped in HCHS/SOL b imputed in HCHS/SOL. All imputation quality in HCHS/SOL >0.9 SNPs in bold had P≤0.05 in combined replication studies ©2019 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc19-0168/-/DC1 SUPPLEMENTARY DATA Supplementary Table S3. Associations of 18 SNPs with HbA1c levels (%) in replication studies Allele SCHS BPRHS BioMe-OMNI BioMe-MEGA SNP Gene Chr Position Effect Other EAF β (SE) P EAF β (SE) P EAF β (SE) P EAF β (SE) P rs113282222 CEP104 1 3718591 TGGAG T 0.161 -0.041 (0.033) 0.218 0.202 0.016 (0.058) 0.785 0.188 0.037 (0.017) 0.031 0.194 -0.047 (0.018) 0.011 rs199584848 TMEM206 1 212544641 A AAG 0.012 0.179 (0.127) 0.159 0.020 -0.305 (0.171) 0.074 NA NA NA NA NA NA rs113119484 CADM2 3 85463419 T G 0.019 -0.057 (0.091) 0.533 0.016 0.168 (0.175) 0.336 0.017 0.011 (0.051) 0.829 0.017 0.034 (0.056) 0.546 rs10513537 IQCJ−SCHIP1 3 158904859 G A 0.267 -0.017 (0.026) 0.522 0.155 0.043 (0.056) 0.445 0.157 0.006 (0.018) 0.725 0.143 0.007 (0.022) 0.739 rs74638476 ETV5 3 185735512 T C 0.003 -0.043 (0.233) 0.854 0.031 -0.011 (0.164) 0.948 0.029 0.003 (0.042) 0.953 0.032 -0.010 (0.041) 0.812 rs73774950 NUDT12 5 102957617 C T 0.003 -0.095 (0.240) 0.691 0.030 0.176 (0.113) 0.119 0.045 -0.014 (0.032) 0.667 0.036 0.043 (0.039) 0.269 rs11752643 HLA−DQA2 6 32669373 T C 0.015 0.066 (0.138) 0.630 NA NA NA 0.021 -0.022 (0.047) 0.645 0.017 0.049 (0.056) 0.377 rs6949071 ETV1 7 13655049 C G 0.420 0.027 (0.026) 0.288 0.489 0.057 (0.038) 0.138 0.492 -0.017 (0.015) 0.275 0.495 0.010 (0.016) 0.538 rs6992753 UNC5D 8 35926402 A G 0.005 0.023 (0.175) 0.897 0.027 0.018 (0.172) 0.915 0.027 -0.011 (0.041) 0.780 0.025 0.056 (0.049) 0.249 rs116781682 FAM188A 10 16218532 T C NA NA NA 0.021 -0.559 (0.165) 0.001 0.019 -0.056 (0.051) 0.274 0.020 0.006 (0.052) 0.915 rs334 HBB 11 5248232 A T 0.005 0.005 (0.182) 0.978 0.020 -1.190 (0.168) 0.000 0.011 0.039 (0.067) 0.562 0.013 -0.138 (0.064) 0.032 rs73393695 FBXO21 12 117644934 A G 0.028 -0.049 (0.092) 0.591 0.076 -0.101 (0.069) 0.144 0.066 -0.022 (0.029) 0.445 0.058 0.057 (0.033) 0.085 rs145546625 HBM 16 220583 T C 0.073 0.079 (0.046) 0.086 0.020 -0.062 (0.208) 0.766 0.027 0.023 (0.041) 0.568 0.041 0.043 (0.035) 0.225 rs144212976 RAB11FIP4 17 29821839 G A 0.032 0.021 (0.069) 0.758 0.011 -0.094 (0.218) 0.666 0.012 -0.049 (0.063) 0.438 0.014 0.000 (0.062) 0.995 rs2748424 TMC6 17 76124865 G C 0.195 0.072 (0.035) 0.038 NA NA NA 0.228 0.026 (0.017) 0.128 0.250 0.027 (0.019) 0.154 rs74575505 SIGLEC12 19 51942103 G A 0.109 -0.012 (0.038) 0.762 0.116 -0.062 (0.060) 0.302 0.115 -0.021 (0.022) 0.320 0.111 0.021 (0.024) 0.380 rs56222990 PDGFB 22 39652947 G C 0.039 0.092 (0.078) 0.234 0.106 0.051 (0.065) 0.437 0.084 0.051 (0.026) 0.051 0.093 -0.041 (0.026) 0.113 rs1050828 G6PD X 153764217 T C NA NA NA 0.026 -0.292 (0.098) 0.003 NA NA NA NA NA NA A1: effect allele; A2: reference allele; EAF: effect allele frequency; Beta: Effect size (%) for each effect allele of SNP on HbA1c.