Online Appendix:
1. Loci identified using variance components methods (LOD2.0) in Pima Indians.
Trait Chrom. cM LOD Reference
Young-Onset T2DM 1 170 2.5 1
Respiratory Quotient 1 105 2.8 2
HDL-Cholesterol 3 181 2.6 3
Leptin 6 54 2.1 4
Young-Onset T2DM 7 120 2.0 1
2-Hour Insulin after OGTT 9 99 2.2 5
Body Mass Index 11 139 3.6 1
Parent of Origin affect on Birth Weight 11 88 3.4 6
Percent Fat 18 54 2.3 2
Total Cholesterol 19 0 3.9 3
Insulin Action 22 0 2.1 5
Fasting Glucose 22 46 2.4 5
2. Genes analyzed as positional candidates for linkage in Pima Indians.
Chromosome 1q21-24 (Young Onset T2DM)
Gene Reference
ENSA 7
IL6R 8
PTGS2 9
MGST3 10
PLA2G4A 11
CRP 12
PRKAB2 13
KCNJ9 14
KCNJ10 15
LMX1A 16
INSRR 17
LMNA 18
PEA15 19
MTG8 20
SLC19A2 21
PBX1 22
PKLR unpublished
RXRG unpublished
MGST3 unpublished
Chromosome 11q23-24 (Body Mass Index)
Gene Reference
DRD2 23
ORP150 24
NCAM unpublished
PLZF unpublished
NNMT unpublished
IGS4 unpublished
ZNF259 unpublished
APOA1 unpublished
APOA3 unpublished
APOA4 unpublished
APOA5 unpublished
TAGLN unpublished
PCSK7 unpublished
ARCN1 unpublished
CBL2 unpublished
C1Q TNF unpublished
THY1 unpublished
ARHGEF12 unpublished
GRIK4 unpublished
SC5DL unpublished
ZNF202 unpublished
SP17 unpublished
NRGN unpublished
BCSC unpublished
TBRG1 unpublished
PANX3 unpublished
CTH unpublished
PKNOX2 unpublished
FEZ unpublished
SP10 unpublished
PIG8 unpublished
NEPH-2 unpublished
ETS-1 unpublished
FLI1 unpublished
KCNJ1 unpublished
KCNJ5 unpublished
KIAA 0712 unpublished
BARX2 unpublished
NFRKB unpublished
APLP2 unpublished
HNT unpublished
OPCML unpublished
B3GAT1 unpublished
Chromosome 7q (Young Onset T2DM)
Gene Reference
PPP1R3 25
Chromosome 19p (Total serum cholesterol)
Gene Reference
LDLR unpublished
Chromosome 11p (Parent of origin effect on birth weight)
Gene Reference
INS 26
References for Online Appendix
1. Hanson RL, Ehm MG, Pettitt DJ, Prochazka M, Thompson DB, Timberlake D, Foroud T, Kobes S, Baier L, Burns DK, Almasy L, Blangero J, Garvey WT, Bennett PH, Knowler WC: An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. Am J Hum Genet. 63:1130-1138, 1998.
2. Norman RA, Tataranni PA, Pratley R, Thompson DB, Hanson RL, Prochazka M, Baier L, Ehm MG, Sakul H, Foroud T, Garvey WT, Burns D, Knowler WC, Bennett PH, Bogardus C, Ravussin E. Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians. Am J Hum Genet. 62: 659-68, 1998.
3. Imperatore G, Knowler WC, Pettitt DJ, Kobes S, Fuller JH, Bennett PH, Hanson RL. A locus influencing total serum cholesterol on chromosome 19p: results from an autosomal genomic scan of serum lipid concentrations in Pima Indians. Arterioscler Thromb Vasc Biol. 20: 2651-6, 2000.
4.Walder K, Hanson RL, Kobes S, Knowler WC, Ravussin E. An autosomal genomic scan for loci linked to plasma leptin concentration in Pima Indians. Int J Obes Relat Metab Disord. 24: 559-65, 2000.
5. Pratley RE, Thompson DB, Prochazka M, Baier L, Mott D, Ravussin E, Sakul H, Ehm MG, Burns DK, Foroud T, Garvey WT, Hanson RL, Knowler WC, Bennett PH, Bogardus C: An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians. J Clin Invest. 101:1757-1764, 1998.
6. Lindsay RS, Kobes S, Knowler WC, Hanson RL. Genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of birth weight. Hum Genet. 110: 503-9, 2002.
7. Thameem F, Farook VS, Yang X, Lee YH, Permana PA, Bogardus C, Prochazka M. The transcribed endosulfine alpha gene is located within a type 2 diabetes-linked region on 1q: sequence and expression analysis in Pima Indians. Mol Genet Metab. 81: 16-21, 2004.
8. Wolford JK, Colligan PB, Gruber JD, Bogardus C. Variants in the interleukin 6 receptor gene are associated with obesity in Pima Indians. Mol Genet Metab. 80: 338-43, 2003.
9. Konheim YL, Wolford JK. Association of a promoter variant in the inducible cyclooxygenase-2 gene (PTGS2) with type 2 diabetes mellitus in Pima Indians. Hum Genet. 113: 377-81, 2003.
10. Thameem F, Yang X, Permana PA, Wolford JK, Bogardus C, Prochazka M. Evaluation of the microsomal glutathione S-transferase 3 (MGST3) locus on 1q23 as a Type 2 diabetes susceptibility gene in Pima Indians. Hum Genet. 113: 353-8, 2003.
11. Wolford JK, Konheim YL, Colligan PB, Bogardus C. Association of a F479L variant in the cytosolic phospholipase A2 gene (PLA2G4A) with decreased glucose turnover and oxidation rates in Pima Indians. Mol Genet Metab. 79: 61-6, 2003.
12. Wolford JK, Gruber JD, Ossowski VM, Vozarova B, Antonio Tataranni P, Bogardus C, Hanson RL. A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians. Mol Genet Metab. 78: 136-44, 2003.
13. Prochazka M, Farook VS, Ossowski V, Wolford JK, Bogardus C. Variant screening of PRKAB2, a type 2 diabetes mellitus susceptibility candidate gene on 1q in Pima Indians. Mol Cell Probes. 16: 421-7, 2002.
14. Wolford JK, Hanson RL, Kobes S, Bogardus C, Prochazka M. Analysis of linkage disequilibrium between polymorphisms in the KCNJ9 gene with type 2 diabetes mellitus in Pima Indians. Mol Genet Metab. 73: 97-103, 2001.
15. Farook VS, Hanson RL, Wolford JK, Bogardus C, Prochazka M. Molecular analysis of KCNJ10 on 1q as a candidate gene for Type 2 diabetes in Pima Indians. Diabetes 51: 3342-6, 2002.
16. Thameem F, Wolford JK, Wang J, German MS, Bogardus C, Prochazka M. Cloning, expression and genomic structure of human LMX1A, and variant screening in Pima Indians. Gene. 290: 217-25, 2002.
17. Wolford JK, Thameem F, Bogardus C, Prochazka M. Polymorphism screening of the insulin receptor-related receptor gene (INSRR) on 1q in Pima Indians. Mol Cell Probes. 15: 223-7, 2001.
18. Wolford JK, Hanson RL, Bogardus C, Prochazka M. Analysis of the lamin A/C gene as a candidate for type II diabetes susceptibility in Pima Indians. Diabetologia. 44: 779-82, 2001.
19. Wolford JK, Bogardus C, Ossowski V, Prochazka M. Molecular characterization of the human PEA15 gene on 1q21-q22 and association with type 2 diabetes mellitus in Pima Indians. Gene. 241: 143-8, 2000.
20. Wolford JK, Bogardus C, Prochazka M. Polymorphism in the 3' untranslated region of MTG8 is associated with obesity in Pima Indian males. Biochem Biophys Res Commun. 246: 624-6, 1998.
21. Thameem F, Wolford JK, Bogardus C, Prochazka M. Analysis of slc19a2, on 1q23.3 encoding a thiamine transporter as a candidate gene for type 2 diabetes mellitus in Pima Indians. Mol Genet Metab. 72: 360-3, 2001.
22. Thameem F, Wolford JK, Bogardus C, Prochazka M. Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians. Biochem Biophys Acta. 1518: 215-20, 2001.
23. Jenkinson CP, Hanson R, Cray K, Wiedrich C, Knowler WC, Bogardus C, Baier L. Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians. Int J Obes Relat Metab Disord. 24: 1233-8, 2000.
24. Kovacs P, Yang X, Permana PA, Bogardus C, Baier LJ. Polymorphisms in the oxygen-regulated protein 150 gene (ORP150) are associated with insulin resistance in Pima Indians. Diabetes. 51: 1618-21, 2002.
25. Xia J, Scherer SW, Cohen PT, Majer M, Xi T, Norman RA, Knowler WC, Bogardus C, Prochazka M. A common variant in PPP1R3 associated with insulin resistance and type 2 diabetes. Diabetes. 47: 1519-24, 1998.
26. Robert S. Lindsay, Robert L. Hanson, Chris Wiedrich, William C. Knowler, Peter H. Bennett, and Leslie J. Baier The insulin gene variable number tandem repeat class I/III polymorphism is in linkage disequilibrium with birth weight but not Type 2 diabetes in the Pima population. Diabetes. 52: 187-93, 2003.
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