Supplemental Table 1. Type 2 Diabetes Risk Variants Examined in Women with PCOS and Controls

Supplemental Table 1. Type 2 Diabetes Risk Variants Examined in Women with PCOS and

Controls

Gene Variant Chr ChrPosition Reference Risk Genotype HWE (NCBI 36) score Call rate P-value ADAMTS9 rs4607103 3 64686944 (1) T2D 1.0 0.801 rs6795735 3 64680405 0.99 0.043 BCL11A rs243021 2 60438323 (1) T2D 1.0 0.574 CDC123/CAMK1 rs12779790 (1) T2D 0.85 0.00030 D (failed) CDKAL1 rs10440833 6 20796100 (2;3) T2D 0.99 1.000 rs7754840 6 20769229 (2;4) 1 0.912 CDKN2A/B rs10965250 9 22123284 (2-4) 0.99 0.280 rs10811661 9 (2-4) T2D 1.0 0.381 CENTD2 rs1552224 11 72110746 (5) T2D 0.99 0.546 CHCHD9 rs13292136 9 81141948 (5) T2D 1.0 0.421 DUSP9 rs5945326 23 152553116 (5) T2D 0.99 0.807 ENPP1/PC1 rs1044498 6 132214061 (6) 1.0 0.254 FTO rs11642841 16 52402988 (3;4) 0.99 0.367 rs9939609 16 52378028 (7) T2D 0.97 0.691

HHEX/IDE rs1111875 10 94452862 (2-4) T2D 1.0 0.213 HMGA2 rs1531343 12 64461161 (5) T2D 1.0 0.087

HNF1A rs7957197 12 119945069 (5) T2D 1.0 0.182 HNF1B rs4430796 17 33172153 1.0 0.575 rs757210 17 33170628 T2D 0.99 0.616 IGF2BP2 rs1470579 (2;4) T2D failed - design IRS1 rs2943641 2 226801989 (8) T2D 1.0 0.614 rs7578326 2 226728897 0.99 0.543 JAZF1 rs849134 7 28162747 0.99 0.135 rs864745 7 28147081 (1) T2D 0.96 0.0021 KCNQ1 rs2237892 11 2796327 (2;4) T2D 1.0 1.000

rs231362 11 2648047 (5) T2D 0.99 0.636

KCNJ11 rs5219 11 17366148 (9) 0.99 1.000 rs5215 11 17365206 (3) T2D 1.0 0.841 KLF14 rs972283 7 130117394 (5) T2D 0.98 0.394 MTNR1B rs1387153 11 92313476 1.0 0.578 rs10830963 11 92348358 (10;11) T2D 1.0 0.241 NOTCH2 rs10923931 1 120319482 (1) T2D 1.0 0.790 PPARG rs13081389 3 12264800 1.0 0.619 rs1801282 3 12368125 (2-4;12) T2D 1.0 1.000 PRC1 rs8042680 15 89322341 (5) T2D 1.0 0.838

SLC30A8 rs13266634 8 118253964 (2-4) T2D 1.0 1.000

rs3802177 0.34 0.081 (failed) TCF7L2 rs7903146 10 114748339 (4;13;14) T2D 0.94 0.738

rs11196236 10 114877712 (15) 1.0 0.505

rs11196229 10 114856162 (15) 1.0 0.235

rs12255372 10 114798892 0.98 0.740 THADA rs11899863 2 43472323 1.0 0.311 rs7578597 2 43586327 (1) T2D 0.98 0.379 rs6544661 2 43565429 0.99 0.153 rs7567607 2 43491689 0.99 0.013 rs12478601 2 43575012 (16) 1.0 0.156 rs7582497 2 43492451 0.99 0.018 rs12468394 2 43414665 (16) 0.99 0.851 rs10186921 2 43498060 0.98 0.295 rs6544659 2 43511927 1.0 0.109 rs6544660 2 43542000 0.99 0.091 rs6751622 2 43569328 1.0 0.254 rs6746064 2 43571154 0.99 0.182

TP53INP1 rs896854 8 96029687 (5) T2D 0.99 0.573 TSPAN8/LGR5 rs4760790 12 69921061 1.0 0.734 rs7961581 12 69949369 (1) T2D 0.95 0.817 WFS1 rs10010131 4 (17) 0.69 1x10-50 (failed) (failed) rs1801214 5 6353923 T2D 0.99 0.557 ZBED3 rs4457053 15 76460705 (5) T2D 1.0 0.394 ZFAND6 rs11634397 8 78219277 (5) T2D 1.0 1.000 Supplementary Table 2. Characteristics of Women with PCOS and Control Subjects

Parameter PCOS Control P value Age (yrs) 28.4±7.0 28.9±8.5 0.3 BMI 30.8±8.6 23.5±3.8 1.7X10-53 Waist Circumference (cm) 96.1±18.9 80.6±10.6 2.5X10-36 Hip Circumference (cm) 108.8±16.9 98.4±9.5 5.6X10-22 WHR 0.88±0.08 0.82±0.06 7.2X10-29 SBP (mmHg) 114.1±15.8 109.5±12.5 1.4X10-6 DBP (mmHg) 71.6±12.2 70.0±9.4 0.03 Pulse (beats per minute) 74.7±10.4 68.3±9.4 8.3X10-20 Testosterone (ng/dL) 64.0±33.5 35.7±17.2 3.8X10-33 SHBG (nmol/L) 41.2±22.1 65.8±31.0 1.5X10-24 Androstenedione (ng/mL) 3.6±1.3 3.1±1.5 0.0001 DHEAS (µg/dL) 197±103 210±107 0.2 LH (IU/L) 26.9±16.7 14.9±12.8 6.9x10-21 FSH (IU/L) 10.5±2.9 10.6±3.6 0.8 LH:FSH 2.6±1.4 1.4±0.9 1.1X10-26 FG Score 12.6±7.6 4.1±2.3 3.3X10-72 HbA1C (%) 5.3±0.3 5.2±0.3 0.0006 Fasting Glucose (mg/dL) 84.9±9.4 80.9±7.3 5.1X10-10 Glucose 120 min (mg/dL) 99.9±28.6 85.2±21.9 4.3X10-13 Fasting Insulin (µIU/mL) 10.6±10.3 5.2±3.7 2.5X10-18 Insulin 120 min (µIU/mL) 60.1±62.4 25.4±17.5 2.0X10-20 HOMA-IR 2.3±2.4 1.0±0.7 1.6X10-18 Glucose/Insulin 14.4±10.5 20.0±9.8 9.8X10-13 Cholesterol (mg/dL) 183.4±35.3 173.9±32.9 0.0004 Triglycerides (mg/dL) 100.6±63.5 67.1±27.4 1.4X10-17 HDL (mg/dL) 52.8±16.3 61.5±14.2 7.4X10-13 LDL (mg/dL) 111.6±32.3 96.1±28.4 1.4X10-10 Ovarian Volume (mL) 15.0±8.0 9.2±4.0 1.7X10-25 Follicle Number 13.5±3.8 9.4±3.3 5.4X10-44 Reference List

1. Zeggini,E, Scott,LJ, Saxena,R, Voight,BF, Marchini,JL, Hu,T, de Bakker,PI, Abecasis,GR, Almgren,P, Andersen,G, Ardlie,K, Bostrom,KB, Bergman,RN, Bonnycastle,LL, Borch- Johnsen,K, Burtt,NP, Chen,H, Chines,PS, Daly,MJ, Deodhar,P, Ding,CJ, Doney,AS, Duren,WL, Elliott,KS, Erdos,MR, Frayling,TM, Freathy,RM, Gianniny,L, Grallert,H, Grarup,N, Groves,CJ, Guiducci,C, Hansen,T, Herder,C, Hitman,GA, Hughes,TE, Isomaa,B, Jackson,AU, Jorgensen,T, Kong,A, Kubalanza,K, Kuruvilla,FG, Kuusisto,J, Langenberg,C, Lango,H, Lauritzen,T, Li,Y, Lindgren,CM, Lyssenko,V, Marvelle,AF, Meisinger,C, Midthjell,K, Mohlke,KL, Morken,MA, Morris,AD, Narisu,N, Nilsson,P, Owen,KR, Palmer,CN, Payne,F, Perry,JR, Pettersen,E, Platou,C, Prokopenko,I, Qi,L, Qin,L, Rayner,NW, Rees,M, Roix,JJ, Sandbaek,A, Shields,B, Sjogren,M, Steinthorsdottir,V, Stringham,HM, Swift,AJ, Thorleifsson,G, Thorsteinsdottir,U, Timpson,NJ, Tuomi,T, Tuomilehto,J, Walker,M, Watanabe,RM, Weedon,MN, Willer,CJ, Illig,T, Hveem,K, Hu,FB, Laakso,M, Stefansson,K, Pedersen,O, Wareham,NJ, Barroso,I, Hattersley,AT, Collins,FS, Groop,L, McCarthy,MI, Boehnke,M, Altshuler,D: Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 40:638-645, 2008 2. Saxena,R, Voight,BF, Lyssenko,V, Burtt,NP, de Bakker,PI, Chen,H, Roix,JJ, Kathiresan,S, Hirschhorn,JN, Daly,MJ, Hughes,TE, Groop,L, Altshuler,D, Almgren,P, Florez,JC, Meyer,J, Ardlie,K, Bengtsson,BK, Isomaa,B, Lettre,G, Lindblad,U, Lyon,HN, Melander,O, Newton- Cheh,C, Nilsson,P, Orho-Melander,M, Rastam,L, Speliotes,EK, Taskinen,MR, Tuomi,T, Guiducci,C, Berglund,A, Carlson,J, Gianniny,L, Hackett,R, Hall,L, Holmkvist,J, Laurila,E, Sjogren,M, Sterner,M, Surti,A, Svensson,M, Svensson,M, Tewhey,R, Blumenstiel,B, Parkin,M, DeFelice,M, Barry,R, Brodeur,W, Camarata,J, Chia,N, Fava,M, Gibbons,J, Handsaker,B, Healy,C, Nguyen,K, Gates,C, Sougnez,C, Gage,D, Nizzari,M, Gabriel,SB, Chirn,GW, Ma,Q, Parikh,H, Richardson,D, Ricke,D, Purcell,S: Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331-1336, 2007 3. Zeggini,E, Weedon,MN, Lindgren,CM, Frayling,TM, Elliott,KS, Lango,H, Timpson,NJ, Perry,JR, Rayner,NW, Freathy,RM, Barrett,JC, Shields,B, Morris,AP, Ellard,S, Groves,CJ, Harries,LW, Marchini,JL, Owen,KR, Knight,B, Cardon,LR, Walker,M, Hitman,GA, Morris,AD, Doney,AS, McCarthy,MI, Hattersley,AT: Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336- 1341, 2007 4. Scott,LJ, Mohlke,KL, Bonnycastle,LL, Willer,CJ, Li,Y, Duren,WL, Erdos,MR, Stringham,HM, Chines,PS, Jackson,AU, Prokunina-Olsson,L, Ding,CJ, Swift,AJ, Narisu,N, Hu,T, Pruim,R, Xiao,R, Li,XY, Conneely,KN, Riebow,NL, Sprau,AG, Tong,M, White,PP, Hetrick,KN, Barnhart,MW, Bark,CW, Goldstein,JL, Watkins,L, Xiang,F, Saramies,J, Buchanan,TA, Watanabe,RM, Valle,TT, Kinnunen,L, Abecasis,GR, Pugh,EW, Doheny,KF, Bergman,RN, Tuomilehto,J, Collins,FS, Boehnke,M: A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341-1345, 2007 5. Voight,BF, Scott,LJ, Steinthorsdottir,V, Morris,AP, Dina,C, Welch,RP, Zeggini,E, Huth,C, Aulchenko,YS, Thorleifsson,G, McCulloch,LJ, Ferreira,T, Grallert,H, Amin,N, Wu,G, Willer,CJ, Raychaudhuri,S, McCarroll,SA, Langenberg,C, Hofmann,OM, Dupuis,J, Qi,L, Segre,AV, van,HM, Navarro,P, Ardlie,K, Balkau,B, Benediktsson,R, Bennett,AJ, Blagieva,R, Boerwinkle,E, Bonnycastle,LL, Bengtsson,BK, Bravenboer,B, Bumpstead,S, Burtt,NP, Charpentier,G, Chines,PS, Cornelis,M, Couper,DJ, Crawford,G, Doney,AS, Elliott,KS, Elliott,AL, Erdos,MR, Fox,CS, Franklin,CS, Ganser,M, Gieger,C, Grarup,N, Green,T, Griffin,S, Groves,CJ, Guiducci,C, Hadjadj,S, Hassanali,N, Herder,C, Isomaa,B, Jackson,AU, Johnson,PR, Jorgensen,T, Kao,WH, Klopp,N, Kong,A, Kraft,P, Kuusisto,J, Lauritzen,T, Li,M, Lieverse,A, Lindgren,CM, Lyssenko,V, Marre,M, Meitinger,T, Midthjell,K, Morken,MA, Narisu,N, Nilsson,P, Owen,KR, Payne,F, Perry,JR, Petersen,AK, Platou,C, Proenca,C, Prokopenko,I, Rathmann,W, Rayner,NW, Robertson,NR, Rocheleau,G, Roden,M, Sampson,MJ, Saxena,R, Shields,BM, Shrader,P, Sigurdsson,G, Sparso,T, Strassburger,K, Stringham,HM, Sun,Q, Swift,AJ, Thorand,B, Tichet,J, Tuomi,T, van Dam,RM, van Haeften,TW, van,HT, van Vliet-Ostaptchouk,JV, Walters,GB, Weedon,MN, Wijmenga,C, Witteman,J, Bergman,RN, Cauchi,S, Collins,FS, Gloyn,AL, Gyllensten,U, Hansen,T, Hide,WA, Hitman,GA, Hofman,A, Hunter,DJ, Hveem,K, Laakso,M, Mohlke,KL, Morris,AD, Palmer,CN, Pramstaller,PP, Rudan,I, Sijbrands,E, Stein,LD, Tuomilehto,J, Uitterlinden,A, Walker,M, Wareham,NJ, Watanabe,RM, Abecasis,GR, Boehm,BO, Campbell,H, Daly,MJ, Hattersley,AT, Hu,FB, Meigs,JB, Pankow,JS, Pedersen,O, Wichmann,HE, Barroso,I, Florez,JC, Frayling,TM, Groop,L, Sladek,R, Thorsteinsdottir,U, Wilson,JF, Illig,T, Froguel,P, van Duijn,CM, Stefansson,K, Altshuler,D, Boehnke,M, McCarthy,MI: Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42:579-589, 2010 6. McAteer,JB, Prudente,S, Bacci,S, Lyon,HN, Hirschhorn,JN, Trischitta,V, Florez,JC: The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European populations: evidence from an updated meta-analysis in 42,042 subjects. Diabetes 57:1125-1130, 2008 7. Barber,TM, Bennett,AJ, Groves,CJ, Sovio,U, Ruokonen,A, Martikainen,H, Pouta,A, Hartikainen,AL, Elliott,P, Lindgren,CM, Freathy,RM, Koch,K, Ouwehand,WH, Karpe,F, Conway,GS, Wass,JA, Jarvelin,MR, Franks,S, McCarthy,MI: Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome. Diabetologia 51:1153-1158, 2008 8. Rung,J, Cauchi,S, Albrechtsen,A, Shen,L, Rocheleau,G, Cavalcanti-Proenca,C, Bacot,F, Balkau,B, Belisle,A, Borch-Johnsen,K, Charpentier,G, Dina,C, Durand,E, Elliott,P, Hadjadj,S, Jarvelin,MR, Laitinen,J, Lauritzen,T, Marre,M, Mazur,A, Meyre,D, Montpetit,A, Pisinger,C, Posner,B, Poulsen,P, Pouta,A, Prentki,M, Ribel-Madsen,R, Ruokonen,A, Sandbaek,A, Serre,D, Tichet,J, Vaxillaire,M, Wojtaszewski,JF, Vaag,A, Hansen,T, Polychronakos,C, Pedersen,O, Froguel,P, Sladek,R: Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet 41:1110-1115, 2009 9. Barber,TM, Bennett,AJ, Gloyn,AL, Groves,CJ, Sovio,U, Ruokonen,A, Martikainen,H, Pouta,A, Taponen,S, Weedon,MN, Hartikainen,AL, Wass,JA, Jarvelin,MR, Zeggini,E, Franks,S, McCarthy,MI: Relationship between E23K (an established type II diabetes- susceptibility variant within KCNJ11), polycystic ovary syndrome and androgen levels. Eur J Hum Genet 15:679-684, 2007 10. Li,C, Shi,Y, You,L, Wang,L, Chen,ZJ: Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome. Mol Hum Reprod 17:193-198, 2011 11. Wang,L, Wang,Y, Zhang,X, Shi,J, Wang,M, Wei,Z, Zhao,A, Li,B, Zhao,X, Xing,Q, He,L: Common genetic variation in MTNR1B is associated with serum testosterone, glucose tolerance, and insulin secretion in polycystic ovary syndrome patients. Fertil Steril 94:2486- 9, 2489, 2010 12. San-Millan,JL, Escobar-Morreale,HF: The role of genetic variation in peroxisome proliferator-activated receptors in the polycystic ovary syndrome (PCOS): an original case- control study followed by systematic review and meta-analysis of existing evidence. Clin Endocrinol (Oxf) 72:383-392, 2010 13. Barber,TM, Bennett,AJ, Groves,CJ, Sovio,U, Ruokonen,A, Martikainen,H, Pouta,A, Hartikainen,AL, Elliott,P, Wass,JA, Jarvelin,MR, Zeggini,E, Franks,S, McCarthy,MI: Disparate genetic influences on polycystic ovary syndrome (PCOS) and type 2 diabetes revealed by a lack of association between common variants within the TCF7L2 gene and PCOS. Diabetologia 50:2318-2322, 2007 14. Grant,SF, Thorleifsson,G, Reynisdottir,I, Benediktsson,R, Manolescu,A, Sainz,J, Helgason,A, Stefansson,H, Emilsson,V, Helgadottir,A, Styrkarsdottir,U, Magnusson,KP, Walters,GB, Palsdottir,E, Jonsdottir,T, Gudmundsdottir,T, Gylfason,A, Saemundsdottir,J, Wilensky,RL, Reilly,MP, Rader,DJ, Bagger,Y, Christiansen,C, Gudnason,V, Sigurdsson,G, Thorsteinsdottir,U, Gulcher,JR, Kong,A, Stefansson,K: Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320-323, 2006 15. Biyasheva,A, Legro,RS, Dunaif,A, Urbanek,M: Evidence for association between polycystic ovary syndrome (PCOS) and TCF7L2 and glucose intolerance in women with PCOS and TCF7L2. J Clin Endocrinol Metab 94:2617-2625, 2009 16. Chen,ZJ, Zhao,H, He,L, Shi,Y, Qin,Y, Shi,Y, Li,Z, You,L, Zhao,J, Liu,J, Liang,X, Zhao,X, Zhao,J, Sun,Y, Zhang,B, Jiang,H, Zhao,D, Bian,Y, Gao,X, Geng,L, Li,Y, Zhu,D, Sun,X, Xu,JE, Hao,C, Ren,CE, Zhang,Y, Chen,S, Zhang,W, Yang,A, Yan,J, Li,Y, Ma,J, Zhao,Y: Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet 43:55-59, 2011 17. Sandhu,MS, Weedon,MN, Fawcett,KA, Wasson,J, Debenham,SL, Daly,A, Lango,H, Frayling,TM, Neumann,RJ, Sherva,R, Blech,I, Pharoah,PD, Palmer,CN, Kimber,C, Tavendale,R, Morris,AD, McCarthy,MI, Walker,M, Hitman,G, Glaser,B, Permutt,MA, Hattersley,AT, Wareham,NJ, Barroso,I: Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet 39:951-953, 2007