Supplementary Data

SUPPLEMENTARY DATA

Title: VARIATION IN SLC19A3 AND PROTECTION FROM MICROVASCULAR DAMAGE IN TYPE 1 DIABETES

Running title: VARIATION IN SLC19A3 AND MICROVASCULAR DAMAGE

Authors: sen Hosseini, Carol Forsblom, Kustaa Hietala, Lorenzo Borio, Valma Harjutsalo, Barbara E. Massimo Porta, Iiro Toppila, Niina Sandholm, S. MohKlein, Ronald Klein, Andrew D. Paterson and Per-Henrik Groop

Supplementary Appendix

Table of Contents

1. The DCCT-EDIC Research Group 2. The FinnDiane Study Group 3. Supplementary Tables

1. The DCCT-EDIC Research Group The members of the DCCT-EDIC Research Group at the time of this publication follow. Study Chairpersons – S. Genuth, D.M. Nathan, B. Zinman (vice-chair), O. Crofford (past)

Clinical Centers Albert Einstein College of Medicine – J. Crandall (past), M. Reid (past), J. Brown-Friday (past), S. Engel (past), J. Sheindlin (past), M. Phillips (past), H. Martinez (past), H. Shamoon (past), H. Engel (past) Case Western Reserve University – R. Gubitosi-Klug, L. Mayer, S. Pendegast, H. Zegarra, D. Miller, L. Singerman, S. Smith-Brewer, M. Novak, J. Quin (past), Saul Genuth (past), M. Palmert (past), E. Brown (past), J. McConnell (past), P. Pugsley (past), P. Crawford (past), W. Dahms (deceased) Weill Cornell Medical College – D. Brillon, M.E. Lackaye, S. Kiss, R. Chan, A. Orlin, M. Rubin, V. Reppucci (past), T. Lee (past), M. Heinemann (past), S. Chang (past), B. Levy (past), L. Jovanovic (past), M. Richardson (past), B. Bosco (past), A. Dwoskin (past), R. Hanna (past), S. Barron (past), R. Campbell (deceased) Henry Ford Health System – F. Whitehouse, D. Kruger, J.K. Jones, P.A. Edwards, A. Bhan, J.D. Carey, E. Angus, A. Thomas, M. McLellan (past), A. Galprin (past) International Diabetes Center – R. Bergenstal, M. Johnson, K. Gunyou, K. Morgan, D. Kendall (past), M. Spencer (past), D. Etzwiler (deceased) Joslin Diabetes Center – L.P. Aiello, E. Golden, P. Arrigg, V. Asuquo, R. Beaser, L. Bestourous, J. Cavallerano, R. Cavicchi, O. Ganda, O. Hamdy, R. Kirby, T. Murtha, D. Schlossman, S. Shah, G. Sharuk, P. Silva, P. Silver, M. Stockman, E. Weimann, H. Wolpert, L.M. Aiello (past), A. Jacobson (past), L. Rand (past), J. Rosenzwieg (past) Massachusetts General Hospital – D.M. Nathan, M.E. Larkin, M. Christofi, K. Folino, J. Godine, P. Lou, C. Stevens, E. Anderson (past), H. Bode (past), S. Brink (past), C. Cornish (past), D. Cros (past), L. Delahanty (past), A. deManbey (past), C. Haggan (past), J. Lynch (past), C. McKitrick (past), D. Norman (past), D. Moore (past), M. Ong (past), C. Taylor (past), D. Zimbler (past), S. Crowell (past), S. Fritz (past), K. Hansen (past), C. Gauthier- Kelly (past) Mayo Foundation – F.J. Service, G. Ziegler, R. Colligan, L. Schmidt (past), B. French (past), R. Woodwick (past), R. Rizza (past), W.F. Schwenk (past), M. Haymond (past), J. Pach (past), J. Mortenson (past), B. Zimmerman (deceased), A. Lucas (deceased) Medical University of South Carolina – L. Luttrell, M. Lopes-Virella, S. Caulder, C. Pittman, N. Patel, K. Lee, M. Nutaitis, J. Fernandes, K. Hermayer, S. Kwon, A. Blevins, J. Parker, J. Colwell (past), D. Lee (past), J. Soule (past), P. Lindsey (past), M. Bracey (past), A. Farr (past), S. Elsing (past), T. Thompson (past), J. Selby (past), T. Lyons (past), S. Yacoub- Wasef (past), M. Szpiech (past), D. Wood (past), R. Mayfield (past) Northwestern University – M. Molitch, B. Schaefer, L. Jampol, A. Lyon, M. Gill, Z. Strugula, L. Kaminski, R. Mirza, E. Simjanoski, D. Ryan, C. Johnson, A. Wallia, S. Ajroud-Driss, P. Astelford, N. Leloudes, A. Degillio University of California, San Diego – O. Kolterman, G. Lorenzi, M. Goldbaum, K. Jones (past), M. Prince (past) , M. Swenson (past), I. Grant (past) , R. Reed (past), R. Lyon (past), M. Giotta (past), T. Clark (past), G. Friedenberg (deceased) University of Iowa – W.I. Sivitz, B. Vittetoe, J. Kramer, M. Bayless (past), R. Zeitler (past), H. Schrott (past), N. Olson (past), L. Snetselaar (past), R. Hoffman (past), J. MacIndoe (past), T. Weingeist (past), C. Fountain (past) University of Maryland School of Medicine – D. Counts, S. Johnsonbaugh, M. Patronas, M. Carney, P. Salemi (past), R. Liss (past), M. Hebdon (past), T. Donner (past), J. Gordon (past), R. Hemady (past), A. Kowarski (past), D. Ostrowski (past), S. Steidl (past), B. Jones (past)

University of Michigan – W.H. Herman, C.L. Martin, R. Pop-Busui, D.A. Greene (past), M.J. Stevens (past), N. Burkhart (past), T. Sandford (past), J. Floyd (deceased) University of Minnesota – J. Bantle, N. Wimmergren, J. Terry, D. Koozekanani, S. Montezuma, B. Rogness (past), M. Mech (past), T. Strand (past), J. Olson (past), L. McKenzie (past), C. Kwong (past), F. Goetz (past), R. Warhol (past) University of Missouri – D. Hainsworth, D. Goldstein, S. Hitt, J. Giangiacomo (deceased) University of New Mexico – D.S. Schade, J.L. Canady, M.R. Burge, A. Das, R.B. Avery, L.H. Ketai, J.E. Chapin, M.L Schluter (past) J. Rich (past), C. Johannes (past), D. Hornbeck (past) University of Pennsylvania – M. Schutta, P.A. Bourne, A. Brucker, S. Braunstein (past), S. Schwartz (past), B.J. Maschak-Carey (past), L. Baker (deceased) University of Pittsburgh – T. Orchard, L. Cimino, T. Songer, B. Doft, S. Olson, D. Becker, D. Rubinstein, R.L. Bergren, J. Fruit, R. Hyre, C. Palmer, N. Silvers (past), L. Lobes (past), P. Paczan Rath (past), P.W. Conrad (past), S. Yalamanchi (past), J.Wesche (past), M. Bratkowksi (past), S. Arslanian (past), J. Rinkoff (past), J. Warnicki (past), D. Curtin (past), D. Steinberg (past), G. Vagstad (past), R. Harris (past), L. Steranchak (past), J. Arch (past), K. Kelly (past), P. Ostrosaka (past), M. Guiliani (past), M. Good (past), T. Williams (past), K. Olsen (past), A. Campbell (past), C. Shipe (past), R. Conwit (past), D. Finegold (past), and M. Zaucha (past), A. Drash (deceased) University of South Florida – A. Morrison, J.I. Malone, M.L. Bernal, P.R. Pavan, N. Grove, E.A. Tanaka (past), D. McMillan (past), J. Vaccaro-Kish (past), L. Babbione (past), H. Solc (past), T.J. DeClue (past) University of Tennessee – S. Dagogo-Jack, C. Wigley, H. Ricks, A. Kitabchi, E. Chaum, M.B. Murphy (past), S. Moser (past), D. Meyer (past), A. Iannacone (past), S. Yoser (past), M. Bryer-Ash (past), S. Schussler (past), H. Lambeth (past) University of Texas Southwestern Medical Center at Dallas – P. Raskin, S. Strowig, M. Basco (past), S. Cercone (deceased) University of Toronto – B. Zinman, A. Barnie, R. Devenyi, M. Mandelcorn, M. Brent, S. Rogers, A. Gordon, N. Bakshi, B. Perkins, L. Tuason, F. Perdikaris, R. Ehrlich (past), D. Daneman (past), K. Perlman (past), S. Ferguson (past) University of Washington – J. Palmer, R. Fahlstrom, I.H.de Boer, J. Kinyoun, L. Van Ottingham, S. Catton (past), J. Ginsberg (past) University of Western Ontario – J. Dupre, C. McDonald, J. Harth, M. Driscoll, T. Sheidow, J. Mahon (past), C. Canny (past), D. Nicolle (past), P. Colby (past), I. Hramiak (past), N.W. Rodger (past), M. Jenner (past), T. Smith (past), W. Brown (past) Vanderbilt University – M. May, J. Lipps Hagan, A. Agarwal, T. Adkins, R. Lorenz (past), S. Feman (past), L. Survant (deceased) Washington University, St. Louis – N.H. White, L. Levandoski, G. Grand, M. Thomas, D. Joseph, K. Blinder, G. Shah, D. Burgess (past), I. Boniuk (deceased), J. Santiago (deceased) Yale University School of Medicine – W. Tamborlane, P. Gatcomb, K. Stoessel, P. Ramos, K. Fong, P. Ossorio, J. Ahern (past) Clinical Coordinating Center Case Western Reserve University – R. Gubitosi-Klug, C. Beck, S. Genuth, J. Quin (past), P. Gaston (past), M. Palmert (past), R. Trail (past), W. Dahms (deceased) Data Coordinating Center George Washington University, The Biostatistics Center – J. Lachin, P. Cleary, J. Backlund, I. Bebu, B. Braffett, L. Diminick, X. Gao, W. Hsu, K. Klumpp, P. McGee (past), W. Sun (past), S. Villavicencio (past), K. Anderson (past), L. Dews (past), Naji Younes (past), B. Rutledge (past), K. Chan (past), D. Rosenberg (past), B. Petty (past), A. Determan (past), D. Kenny (past), C. Williams (deceased)

National Institute of Diabetes and Digestive and Kidney Disease National Institute of Diabetes and Digestive and Kidney Disease Program Office – C. Cowie, C. Siebert (past)

Central Units Central Biochemistry Laboratory (University of Minnesota) – M. Steffes, V. Arends, J. Bucksa (past), M. Nowicki (past), B. Chavers (past) Central Carotid Ultrasound Unit (New England Medical Center) – D. O’Leary, J. Polak, A.Harrington, L. Funk (past) Central ECG Reading Unit (University of Minnesota) – R. Crow (past), B. Gloeb (past), S. Thomas (past), C. O’Donnell (past) Central ECG Reading Unit (Wake Forest University) – E. Soliman, Z.M. Zhang, C. Campbell, L. Keasler, S. Hensley, R. Prineas (past) Central Neurologic Reading Center (University of Michigan, Mayo Clinic, Southern Illinois University) – E.L. Feldman (past), J.W. Albers (past), P. Low (past), C. Sommer (past), K. Nickander (past), T. Speigelberg (past), M. Pfiefer (past), M. Schumer (past), M. Moran (past), J. Farquhar (past) Central Neuropsychological Coding Unit (University of Pittsburgh) – C. Ryan (past), D. Sandstrom (past), T. Williams (past), M. Geckle (past), E. Cupelli (past), F. Thoma (past), B. Burzuk (past), T. Woodfill (past) Central Ophthalmologic Reading Center (University of Wisconsin) – R. Danis, B. Blodi, D. Lawrence, H. Wabers, S. Gangaputra (past), S. Neill (past), M. Burger (past), J. Dingledine (past), V. Gama (past), R. Sussman (past), M. Davis (past), L. Hubbard (past) Computed Tomography Reading Center (Harbor UCLA Research and Education Institute) – M. Budoff, S. Darabian, P. Rezaeian, N. Wong (past), M. Fox (past), R. Oudiz (past), L. Kim (past), R. Detrano (past) Audiometry Reading Center (EpiSense, University of Wisconsin) – K. Cruickshanks, D. Dalton, K. Bainbridge (National Institute on Deafness and Other Communication Disorders) Cardiac MR Reading Center (Johns Hopkins University, National Heart Lung and Blood Institute) – J. Lima, D. Bluemke, E. Turkbey, R. J. van der Geest (past), C. Liu (past), A. Malayeri (past), A. Jain (past), C. Miao (past), H. Chahal (past), R. Jarboe (past) Editor, EDIC Publications – D.M. Nathan

Collaborators Advanced Glycation End Products (Case Western Reserve University) – V. Monnier, D. Sell, C. Strauch Biomarkers (Cleveland Clinic) – S. Hazen, A. Pratt, W. Tang Central Obesity Study (University of Washington) – J. Brunzell, J. Purnell Epigenetics (Beckman Research Institute of City of Hope Medical Center) – R. Natarajan, F. Miao, L. Zhang, Z. Chen Genetic Studies (Hospital for Sick Children) – A. Paterson, A. Boright, S. Bull, L. Sun, S. Scherer (past) Molecular Risk Factors Program Project (Medical University of South Carolina) – M. Lopes-Virella, T.J. Lyons, A. Jenkins, R. Klein, G. Virella, A. Jaffa, R. Carter, J. Stoner, W.T. Garvey (past), D. Lackland (past), M. Brabham (past), D. McGee (past), D. Zheng (past), R. K. Mayfield (past) SCOUT (Veralight) – J. Maynard (past) UroEDIC (University of Washington, University of Michigan) – H. Wessells, A. Sarma, A. Jacobson, R. Dunn, S. Holt, J. Hotaling, C. Kim, Q. Clemens, J. Brown (past), K. McVary (past)

2. The FinnDiane Study Group

Physicians and nurses participating in the collection of FinnDiane participants Anjalankoski Health Center – S. Koivula and T. Uggeldahl Central Finland Central Hospital – T. Forslund, A. Halonen, A. Koistinen, P. Koskiaho, M. Laukkanen, J. Saltevo and M. Tiihonen Central Hospital of Åland Islands – M. Forsen, H. Granlund, A.-C. Jonsson and B. Nyroos Central Hospital of Kanta-Häme – P. Kinnunen, A. Orvola, T. Salonen and A. Vähänen Central Hospital of Kymenlaakso – R. Paldanius, M. Riihelä and L. Ryysy Central Hospital of Länsi-Pohja – H. Laukkanen, P. Nyländen and A. Sademies Central Ostrobothnian Hospital District – S. Anderson, B. Asplund, U. Byskata, P. Liedes, M. Kuusela and T. Virkkala City of Espoo Health Center – (Espoonlahti): A. Nikkola and E. Ritola (Tapiola): M. Niska and H. Saarinen (Viherlaakso): A. Lyytinen City of Helsinki Health Center – (Puistola): H. Kari and T. Simonen (Suutarila): A. Kaprio, J. Kärkkäinen and B. Rantaeskola (Töölö): P. Kääriäinen, J. Haaga and A-L. Pietiläinen City of Hyvinkää Health Center – S. Klemetti, T. Nyandoto, E. Rontu and S. Satuli-Autere City of Vantaa Health Center – (Korso): R. Toivonen and H. Virtanen (Länsimäki): R. Ahonen, M. Ivaska-Suomela and A. Jauhiainen (Martinlaakso): M. Laine, T. Pellonpää and R. Puranen (Myyrmäki): A. Airas, J. Laakso and K. Rautavaara (Rekola): M. Erola and E. Jatkola (Tikkurila): R. Lönnblad, A. Malm, J. Mäkelä and E. Rautamo Heinola Health Center – P. Hentunen and J. Lagerstam Helsinki University Central Hospital (Department of Medicine, Division of Nephrology) – A. Ahola, M. Feodoroff, D. Gordin, O. Heikkilä, K Hietala, S. Hägg, J. Kytö, R. Lithovius, S. Lindh, M. Parkkonen, K. Pettersson-Fernholm, M. Rahkonen, M. Rosengård-Bärlund, A. Sandelin, A-R Salonen, L. Salovaara, M. Saraheimo, T. Soppela, A. Soro-Paavonen, L. Thorn, H. Tikkanen, N. Tolonen, J. Tuomikangas, J. Wadén Herttoniemi Hospital – V. Sipilä Hospital of Lounais-Häme – T. Kalliomäki, J. Koskelainen, R. Nikkanen, N. Savolainen, H. Sulonen and E. Valtonen Iisalmi Hospital – E. Toivanen Jokilaakso Hospital – A. Parta and I. Pirttiniemi Jorvi Hospital – S. Aranko, S. Ervasti, R. Kauppinen-Mäkelin, A. Kuusisto, T. Leppälä, K. Nikkilä and L. Pekkonen Jyväskylä Health Center – K. Nuorva and M. Tiihonen Kainuu Central Hospital – S. Jokelainen, P. Kemppainen, A-M. Mankinen and M. Sankari Kerava Health Center – H. Stuckey and P. Suominen Kirkkonummi Health Center – A. Lappalainen, M. Liimatainen and J. Santaholma Kivelä Hospital – A. Aimolahti and E. Huovinen Koskela Hospital – V. Ilkka and M. Lehtimäki Kotka Health Center – E. Pälikkö-Kontinen and A. Vanhanen Kouvola Health Center – E. Koskinen and T. Siitonen Kuopio University Hospital – E. Huttunen, R. Ikäheimo, P. Karhapää, P. Kekäläinen, M. Laakso, T. Lakka, E. Lampainen, L. Moilanen, L. Niskanen, U. Tuovinen, I. Vauhkonen and E. Voutilainen Kuusamo Health Center – T. Kääriäinen and E. Isopoussu Kuusankoski Hospital – E. Kilkki, I. Koskinen and L. Riihelä Laakso Hospital, Helsinki – T. Meriläinen, P. Poukka, R. Savolainen and N. Uhlenius Lahti City Hospital – A. Mäkelä and M. Tanner

Lapland Central Hospital – L. Hyvärinen, S. Severinkangas and T. Tulokas Lappeenranta Health Center – P. Linkola and I. Pulli Lohja Hospital – T. Granlund, M. Saari and T. Salonen Länsi-Uusimaa Hospital – I.-M. Jousmaa and J. Rinne Loimaa Health Center – A. Mäkelä and P. Eloranta Malmi Hospital – H. Lanki, S. Moilanen and M. Tilly-Kiesi Mikkeli Central Hospital – A. Gynther, R. Manninen, P. Nironen, M. Salminen and T. Vänttinen Mänttä Regional Hospital – I. Pirttiniemi and A-M. Hänninen North Karelian Hospital – U-M. Henttula, P. Kekäläinen, M. Pietarinen, A. Rissanen and M. Voutilainen Nurmijärvi Health Center – A. Burgos and K. Urtamo Oulaskangas Hospital – E. Jokelainen, P.-L. Jylkkä, E. Kaarlela and J. Vuolaspuro Oulu Health Center – L. Hiltunen, R. Häkkinen and S. Keinänen-Kiukaanniemi Oulu University Hospital – R. Ikäheimo Päijät-Häme Central Hospital – H. Haapamäki, A. Helanterä, S. Hämäläinen, V. Ilvesmäki and H. Miettinen Palokka Health Center – P. Sopanen and L. Welling Pieksämäki Hospital – V. Javtsenko and M. Tamminen Pietarsaari Hospital – M-L. Holmbäck, B. Isomaa and L. Sarelin Pori City Hospital – P. Ahonen, P. Merensalo and K. Sävelä Porvoo Hospital – M. Kallio, B. Rask and S. Rämö Raahe Hospital – A. Holma, M. Honkala, A. Tuomivaara and R. Vainionpää Rauma Hospital – K. Laine, K. Saarinen and T. Salminen Riihimäki Hospital – P. Aalto, E. Immonen and L. Juurinen Salo Hospital – A. Alanko, J. Lapinleimu, P. Rautio and M. Virtanen Satakunta Central Hospital – M. Asola, M. Juhola, P. Kunelius, M.-L. Lahdenmäki, P. Pääkkönen and M. Rautavirta Savonlinna Central Hospital – T. Pulli, P. Sallinen, M. Taskinen, E. Tolvanen, H. Valtonen and A. Vartia Seinäjoki Central Hospital – E. Korpi-Hyövälti, T. Latvala and E. Leijala South Karelia Central Hospital – T. Ensala, E. Hussi, R. Härkönen, U. Nyholm and J. Toivanen Tampere Health Center – A. Vaden, P. Alarotu, E. Kujansuu, H. Kirkkopelto-Jokinen, M. Helin, S. Gummerus, L. Calonius, T. Niskanen, T. Kaitala and T. Vatanen Tampere University Hospital – I. Ala-Houhala, T. Kuningas, P. Lampinen, M. Määttä, H. Oksala, T. Oksanen, K. Salonen, H. Tauriainen and S. Tulokas Tiirismaa Health Center – T. Kivelä, L. Petlin and L. Savolainen Turku Health Center – I. Hämäläinen, H. Virtamo and M. Vähätalo Turku University Central Hospital – K. Breitholz, R. Eskola, K. Metsärinne, U. Pietilä, P. Saarinen, R. Tuominen and S. Äyräpää Vaajakoski Health Center – K. Mäkinen and P. Sopanen Valkeakoski Regional Hospital – S. Ojanen, E. Valtonen, H. Ylönen, M. Rautiainen and T. Immonen Vammala Regional Hospital – I. Isomäki, R. Kroneld and M. Tapiolinna-Mäkelä Vaasa Central Hospital – S. Bergkulla, U. Hautamäki, V.-A. Myllyniemi and I. Rusk.

3. Supplementary Tables

Supplementary Table S1. Clinical characteristics of participants included in analysis of the combined phenotype of both diabetic retinopathy and end-stage renal disease

No/mild DR + Normal Severe DR + ESRD P Value* AER / Microalbuminuria Gender 369 (217/152) 190 (76/114) <0.001 (Male/Female) Mean ± SD Missing Mean ± SD Missing Age [yr] 45.4 ± 8.5 - 40.8 ± 10 - <0.001 Duration [yr] 33.1 ± 8.4 - 28.0 ± 6.7 - <0.001 HbA [%] 8.7 ± 3.7 8.1 ± 3.3 1c 9 - <0.001 (mmol/mol) (71.8 ± 17) (65.1 ± 13) BMI 24.1 ± 3.9 63 25.3 ± 3.2 - <0.001 TG [mmol/l] 1.71 ± 1.0 16 1.07 ± 0.6 - <0.001 SBP [mmHg] 153 ± 24 76 132 ± 18 1 <0.001 DBP [mmHg] 85 ± 12 78 78 ± 9 1 <0.001

*p-values for distribution differences between groups. p-value for sex evaluated using Pearson’s Chi- squared test (1 df) and p-values for continuous traits are evaluated using Welch Two Sample t-test. DR: Diabetic retinopathy ESRD: End-stage renal disease AER: albumin excretion rate TG: Serum triglycerides SBP: Systolic blood pressure DBP: Diastolic blood pressure

Supplementary Table S2. Results of expanded models in analysis of both diabetic retinopathy and combined phenotype of diabetic retinopathy and end-stage renal disease

N MAF Phenotype SNP Model Cases Controls Cases Controls OR* [CI 95%] P Value

1a 1566 218 0.142 0.218 0.51 [0.38 - 0.68] 3.81×10-6

1b 1255 216 0.139 0.218 0.50 [0.37 - 0.67] 2.85×10-6 2 1356 218 0.139 0.218 0.49 [0.36 - 0.66] 2.30×10-6

3 1346 218 0.139 0.218 0.49 [0.36 - 0.66] 3.72×10-6 rs12694743 4 1255 216 0.139 0.218 0.49 [0.36 - 0.66] 4.82×10-6 DR

1a 1566 218 0.154 0.213 0.41 [0.28 - 0.60] 3.15×10-6

1b 1255 216 0.153 0.213 0.40 [0.27 - 0.58] 2.49×10-6 2 1356 218 0.152 0.213 0.40 [0.27 - 0.58] 2.56×10-6 -6

rs6713116 3 1346 218 0.152 0.213 0.39 [0.26 - 0.58] 2.80×10 4 1255 216 0.153 0.213 0.38 [0.25 - 0.57] 2.60×10-6

1a 369 190 0.122 0.228 0.31 [0.21 - 0.48] 7.51×10-8

1b 273 189 0.120 0.229 0.30 [0.19 - 0.47] 3.05×10-7 2 298 190 0.118 0.228 0.28 [0.17 - 0.45] 1.29×10-7

3 294 190 0.116 0.228 0.19 [0.11 - 0.34] 1.41×10-8 rs12694743 4 273 189 0.120 0.229 0.15 [0.08 - 0.29] 9.56×10-9 DR+ESRD

1a 369 190 0.140 0.218 0.26 [0.15 - 0.44] 7.49×10-7

1b 273 189 0.139 0.218 0.25 [0.14 - 0.45] 3.35×10-6 2 298 190 0.138 0.218 0.23 [0.13 - 0.42] 1.90×10-6

3 294 190 0.136 0.218 0.15 [0.07 - 0.30] 1.51×10-7 rs6713116 4 273 189 0.139 0.218 0.10 [0.04 - 0.23] 3.56×10-8

Models: 1a: Adjusted for age, sex, duration of diabetes, first 10 PCs 1b: model 1a using only participants with non-missing data for all covariates used in model 4 2: model 1a + log(BMI) and HbA1c 3: model 2 + log(TG) 4: model 3 + SBP and DBP

* Odds ratio of logistic regression for each copy of minor allele

MAF: Minor Allele Frequency DR: Diabetic retinopathy ESRD: End-stage renal disease

Supplementary Table S3. Association of top SNPs and significant covariates used in adjusted models in all genotyped FinnDiane participants with non-missing data

rs12694743 rs6713116 Covariate beta* SE P Value beta* SE P Value N HbA 1c 0.26 0.96 0.78 0.97 1.25 0.44 3347 [mmol/mol] BMI -0.25 0.15 0.10 -0.22 0.19 0.25 3044 TG [mmol/l] 0.05 0.04 0.20 0.06 0.05 0.17 3257 SBP [mmHg] 0.93 0.78 0.23 0.82 1.01 0.42 3272 DBP [mmHg] 0.22 0.40 0.59 0.29 0.52 0.58 3268

*Regression coefficient from linear regression giving increase in absolute values for every copy of minor allele

SE: Standard error for regression coefficient TG: Serum triglycerides SBP: Systolic blood pressure DBP: Diastolic blood pressure

Supplementary Table S4. Association of top SNPs and significant covariates used in adjusted models in subsample of participants used in analysis of combined phenotype of diabetic retinopathy and end-stage renal disease with complete data (N=462)

rs12694743 rs6713116 Covariate beta* SE P Value beta* SE P Value HbA 1c 2.21 1.48 0.14 2.35 1.88 0.21 [mmol/mol] BMI 0.28 0.36 0.45 0.29 0.46 0.53 TG [mmol/l] 0.05 0.08 0.56 0.00 0.10 0.99 SBP [mmHg] 2.37 2.37 0.32 0.39 3.02 0.90 DBP [mmHg] 0.12 1.13 0.91 -0.33 1.44 0.82

*Regression coefficient from linear regression giving increase in absolute values for every copy of minor allele

SE: Standard error for regression coefficient TG: Serum triglycerides SBP: Systolic blood pressure DBP: Diastolic blood pressure