Fine-mapping diabetes-related traits, including insulin resistance, in heterogeneous stock rats

Physiological Genomics

Volumn 44, Issue 21, 2012, Pages 1013-1026

  Solberg Woods, Leah C ^a   Holl, Katie L ^a   Oreper, Daniel ^b   Xie, Yuying ^b   Tsaih, Shirng Wern ^a   Valdar, William ^b  

^a MEDICAL COLLEGE OF WISCONSIN   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Glucose tolerance; Metabolism; Obesity; Type 2 diabetes

Indexed keywords

DNA; GLUCOSE; INSULIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHROMOSOME 1; DIABETES MELLITUS; GENE LINKAGE DISEQUILIBRIUM; GENE MAPPING; GENOTYPE; GLUCOSE BLOOD LEVEL; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; QUANTITATIVE TRAIT LOCUS; RAT; REGRESSION ANALYSIS; STATISTICAL MODEL;

ANIMALS; CHROMOSOME MAPPING; CHROMOSOMES, MAMMALIAN; DIABETES MELLITUS, TYPE 2; DISEASE MODELS, ANIMAL; GENOTYPE; GLUCOSE; INSULIN; INSULIN RESISTANCE; MALE; PHENOTYPE; QUANTITATIVE TRAIT LOCI; RATS; RATS, INBRED ACI; RATS, INBRED WKY;

RATTUS;

EID: 84868566945     PISSN: 10948341     EISSN: 15312267     Source Type: Journal    
DOI: 10.1152/physiolgenomics.00040.2012     Document Type: Article

References (82)

1. Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JD, Hua K, Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SN, Collins FS, Yang IV, Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan L, Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R, Iraqi FA, Pomp D, Threadgill D, de Villena FP, Churchill GA. Genetic analysis of complex traits in the emerging Collaborative Cross. Genome Res 21: 1213-1222, 2011.
2. Bates D, Maechler M, Bolker B. lme4: linear mixed-effects models using S4 classes. R package version 0.999375-40, 2011, http://CRAN.Rproject. org/package_lme4.
3. Billings LK, Florez JC. The genetics of type 2 diabetes: what have we learned from GWAS? Ann NY Acad Sci 1212: 59-77, 2010.
4. Boini KM, Graf D, Hennige AM, Koka S, Kempe DS, Wang K, Ackermann TF, Foller M, Vallon V, Pfeifer K, Schleicher E, Ullrich S, Haring HU, Haussinger D, Lang F. Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1. Am J Physiol Regul Integr Comp Physiol 296: R1695-R1701, 2009.
5. Box GEP, Cox DR. An analysis of transformations (with discussion). J Roy Stat Soc B26: 211-252, 1964.
6. Broman KW, Sen S. A Guide to QTL Mapping with R/qtl. New York: Springer, 2009.
7. Cacho J, Sevillano J, de Castro J, Herrera E, Ramos MP. Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague-Dawley rats. Am J Physiol Endocrinol Metab 295: E1269-E1276, 2008.
8. Calderari S, Gangnerau MN, Thibault M, Meile MJ, Kassis N, Alvarez C, Portha B, Serradas P. Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto-Kakizaki rat model of type 2 diabetes. Diabetologia 50: 1463-1471, 2007.
9. Chang YC, Chiu YF, Liu PH, Shih KC, Lin MW, Sheu WH, Quertermous T, Curb JD, Hsiung CA, Lee WJ, Lee PC, Chen YT, Chuang LM. Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort. Clin Endocrinol (Oxf) 76: 365-372, 2012.
10. Cheng R, Lim JE, Samocha KE, Sokoloff G, Abney M, Skol AD, Palmer AA. Genome-wide association studies and the problem of relatedness among advanced intercross lines and other highly recombinant populations. Genetics 185: 1033-1044, 2010.
11. Chung WK, Zheng M, Chua M, Kershaw E, Power-Kehoe L, Tsuji M, Wu-Peng XS, Williams J, Chua SC Jr, Leibel RL. Genetic modifiers of Leprfa associated with variability in insulin production and susceptibility to NIDDM. Genomics 41: 332-344, 1997.
12. Collaborative Cross Consortium. The genome architecture of the Collaborative Cross mouse genetic reference population. Genetics 190: 389-401, 2012.
13. Collins SC, Wallis RH, Wilder SP, Wallace KJ, Argoud K, Kaisaki PJ, Bihoreau MT, Gauguier D. Mapping diabetes QTL in an intercross derived from a congenic strain of the Brown Norway and Goto-Kakizaki rats. Mamm Genome 17: 538-547, 2006.
14. Devedjian JC, George M, Casellas A, Pujol A, Visa J, Pelegrin M, Gros L, Bosch F. Transgenic mice overexpressing insulin-like growth factor-II in beta cells develop type 2 diabetes. J Clin Invest 105: 731-740, 2000.
15. Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, Wheeler E, Glazer NL, Bouatia-Naji N, Gloyn AL, Lindgren CM, Magi R, Morris AP, Randall J, Johnson T, Elliott P, Rybin D, Thorleifsson G, Steinthorsdottir V, Henneman P, Grallert H, Dehghan A, Hottenga JJ, Franklin CS, Navarro P, Song K, Goel A, Perry JR, Egan JM, Lajunen T, Grarup N, Sparso T, Doney A, Voight BF, Stringham HM, Li M, Kanoni S, Shrader P, Cavalcanti-Proenca C, Kumari M, Qi L, Timpson NJ, Gieger C, Zabena C, Rocheleau G, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, McCarroll SA, Payne F, Roccasecca RM, Pattou F, Sethupathy P, Ardlie K, Ariyurek Y, Balkau B, Barter P, Beilby JP, Ben-Shlomo Y, Benediktsson R, Bennett AJ, Bergmann S, Bochud M, Boerwinkle E, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Bottcher Y, Brunner E, Bumpstead SJ, Charpentier G, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Cornelis M, Crawford G, Crisponi L, Day IN, de Geus EJ, Delplanque J, Dina C, Erdos MR, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Fox CS, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Groves CJ, Grundy S, Gwilliam R, Gyllensten U, Hadjadj S, Hallmans G, Hammond N, Han X, Hartikainen AL, Hassanali N, Hayward C, Heath SC, Hercberg S, Herder C, Hicks AA, Hillman DR, Hingorani AD, Hofman A, Hui J, Hung J, Isomaa B, Johnson PR, Jørgensen T, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Lyssenko V, Mahley R, Mangino M, Manning AK, Martínez-Larrad MT, McAteer JB, McCulloch LJ, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Morken MA, Mukherjee S, Naitza S, Narisu N, Neville MJ, Oostra BA, Orrù M, Pakyz R, Palmer CN, Paolisso G, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rathmann W, Rayner NW, Rice K, Ripatti S, Rivadeneira F, Roden M, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Scott LJ, Seedorf U, Sharp SJ, Shields B, Sigurethsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Thorand B, Tichet J, Tönjes A, Tuomi T, Uitterlinden AG, van Dijk KW, van Hoek M, Varma D, Visvikis-Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Walters GB, Ward KL, Watkins H, Weedon MN, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zeggini E, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC; DIAGRAM Consortium; GIANT Consortium; Global BPgen Consortium, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Hattersley AT, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano-Ríos M, Morris AD, Lind L, Palmer LJ, Hu FB, Franks PW, Ebrahim S, Marmot M, Kao WH, Pankow JS, Sampson MJ, Kuusisto J, Laakso M, Hansen T, Pedersen O, Pramstaller PP, Wichmann HE, Illig T, Rudan I, Wright AF, Stumvoll M, Campbell H, Wilson JF; Anders Hamsten on behalf of Procardis Consortium; MAGIC investigators, Bergman RN, Buchanan TA, Collins FS, Mohlke KL, Tuomilehto J, Valle TT, Altshuler D, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Frayling TM, Ferrucci L, Kong A, Thorsteinsdottir U, Stefansson K, van Duijn CM, Aulchenko YS, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Abecasis GR, Wareham NJ, Sladek R, Froguel P, Watanabe RM, Meigs JB, Groop L, Boehnke M, McCarthy MI, Florez JC, Barroso I. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42: 105-116, 2010.
16. Dupuis J, Siegmund D. Statistical methods for mapping quantitative trait loci from a dense set of markers. Genetics 151: 373-386, 1999.
17. Durrant C, Mott R. Bayesian quantitative trait locus mapping using inferred haplotypes. Genetics 184: 839-852, 2010.
18. Florez JC. Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: Where are the insulin resistance genes? Diabetologia 51: 1100-1110, 2008.
19. Galli J, Fakhrai-Rad H, Kamel A, Marcus C, Norgren S, Luthman H. Pathophysiological and genetic characterization of the major diabetes locus in GK rats. Diabetes 48: 2463-2470, 1999.
20. Galli J, Li LS, Glaser A, Ostenson CG, Jiao H, Fakhrai-Rad H, Jacob HJ, Lander ES, Luthman H. Genetic analysis of non-insulin dependent diabetes mellitus in the GK rat. Nat Genet 12: 31-37, 1996.
21. Gauguier D, Froguel P, Parent V, Bernard C, Bihoreau MT, Portha B, James MR, Penicaud L, Lathrop M, Ktorza A. Chromosomal mapping of genetic loci associated with non-insulin dependent diabetes in the GK rat. Nat Genet 12: 38-43, 1996.
22. Granhall C, Park HB, Fakhrai-Rad H, Luthman H. High-resolution quantitative trait locus analysis reveals multiple diabetes susceptibility loci mapped to intervals-800 kb in the species-conserved Niddm1i of the GK rat. Genetics 174: 1565-1572, 2006.
23. Hansen C, Spuhler K. Development of the National Institutes of Health genetically heterogeneous rat stock. Alcohol Clin Exp Res 8: 477-479, 1984.
24. Hastie T, Tibshirani R, Friedman J. The Elements of Statistical Learning: Data Mining, Inference, and Prediction (2nd edition). New York: Springer, 2009.
25. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world-a growing challenge. N Engl J Med 356: 213-215, 2007.
26. Hu C, Zhang R, Wang C, Wang J, Ma X, Hou X, Lu J, Yu W, Jiang F, Bao Y, Xiang K, Jia W. Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 are associated with glucose metabolism in the Chinese. PLoS One 5: e15542, 2010.
27. Ikeda H, Shino A, Matsuo T, Iwatsuka H, Suzuoki Z. A new genetically obese-hyperglycemic rat (Wistar fatty). Diabetes 30: 1045-1050, 1981.
28. Ingelsson E, Langenberg C, Hivert MF, Prokopenko I, Lyssenko V, Dupuis J, Magi R, Sharp S, Jackson AU, Assimes TL, Shrader P, Knowles JW, Zethelius B, Abbasi FA, Bergman RN, Bergmann A, Berne C, Boehnke M, Bonnycastle LL, Bornstein SR, Buchanan TA, Bumpstead SJ, Bottcher Y, Chines P, Collins FS, Cooper CC, Dennison EM, Erdos MR, Ferrannini E, Fox CS, Graessler J, Hao K, Isomaa B, Jameson KA, Kovacs P, Kuusisto J, Laakso M, Ladenvall C, Mohlke KL, Morken MA, Narisu N, Nathan DM, Pascoe L, Payne F, Petrie JR, Sayer AA, Schwarz PE, Scott LJ, Stringham HM, Stumvoll M, Swift AJ, Syvanen AC, Tuomi T, Tuomilehto J, Tonjes A, Valle TT, Williams GH, Lind L, Barroso I, Quertermous T, Walker M, Wareham NJ, Meigs JB, McCarthy MI, Groop L, Watanabe RM, Florez JC. Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans. Diabetes 59: 1266-1275, 2010.
29. Jensen DR, Ramirez DE. Anomalies in the foundations of ridge regression. Int Stat Rev 76: 89-105, 2008.
30. Jensen DR, Ramirez DE. Surrogate models in ill-conditioned systems. J Stat Plan Inf 140: 2069-2077, 2010.
31. Johannesson M, Lopez-Aumatell R, Stridh P, Diez M, Tuncel J, Blazquez G, Martinez-Membrives E, Canete T, Vicens-Costa E, Graham D, Copley RR, Hernandez-Pliego P, Beyeen AD, Ockinger J, Fernandez-Santamaria C, Gulko PS, Brenner M, Tobena A, Guitart-Masip M, Gimenez-Llort L, Dominiczak A, Holmdahl R, Gauguier D, Olsson T, Mott R, Valdar W, Redei EE, Fernandez-Teruel A, Flint J. A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: the NIH heterogeneous stock. Genome Res 19: 150-158, 2009.
32. Johnsen AK, Valdar W, Golden L, Ortiz-Lopez A, Hitzemann R, Flint J, Mathis D, Benoist C. Genome-wide and species-wide dissection of the genetics of arthritis severity in heterogeneous stock mice. Arthritis Rheum 63: 2630-2640, 2011.
33. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444: 840-846, 2006.
34. Kanemoto N, Hishigaki H, Miyakita A, Oga K, Okuno S, Tsuji A, Takagi T, Takahashi E, Nakamura Y, Watanabe TK. Genetic dissection of "OLETF", a rat model for non-insulin-dependent diabetes mellitus. Mamm Genome 9: 419-425, 1998.
35. Katayama S, Inaba M, Maruno Y, Morita T, Awata T, Oka Y. Glucose intolerance in spontaneously hypertensive and Wistar-Kyoto rats: enhanced gene expression and synthesis of skeletal muscle glucose transporter 4. Hypertens Res 20: 279-286, 1997.
36. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85: 2402-2410, 2000.
37. Kennedy BW, Quinton M, van Arendonk JA. Estimation of effects of single genes on quantitative traits. J Anim Sci 70: 2000-2012, 1992.
38. Kooner JS, Saleheen D, Sim X, Sehmi J, Zhang W, Frossard P, Been LF, Chia KS, Dimas AS, Hassanali N, Jafar T, Jowett JB, Li X, Radha V, Rees SD, Takeuchi F, Young R, Aung T, Basit A, Chidambaram M, Das D, Grundberg E, Hedman AK, Hydrie ZI, Islam M, Khor CC, Kowlessur S, Kristensen MM, Liju S, Lim WY, Matthews DR, Liu J, Morris AP, Nica AC, Pinidiyapathirage JM, Prokopenko I, Rasheed A, Samuel M, Shah N, Shera AS, Small KS, Suo C, Wickremasinghe AR, Wong TY, Yang M, Zhang F, Abecasis GR, Barnett AH, Caulfield M, Deloukas P, Frayling TM, Froguel P, Kato N, Katulanda P, Kelly MA, Liang J, Mohan V, Sanghera DK, Scott J, Seielstad M, Zimmet PZ, Elliott P, Teo YY, McCarthy MI, Danesh J, Tai ES, Chambers JC. Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet 43: 984-989, 2011.
39. Kover PX, Valdar W, Trakalo J, Scarcelli N, Ehrenreich IM, Purugganan MD, Durrant C, Mott R. A multiparent advanced generation inter-cross to fine-map quantitative traits in Arabidopsis thaliana. PLoS Genet 5: e1000551, 2009.
40. Kulkarni RN. New insights into the roles of insulin/IGF-I in the development and maintenance of beta-cell mass. Rev Endocr Metab Disord 6: 199-210, 2005.
41. Lander ES, Botstein D. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121: 185-199, 1989.
42. Lin JM, Ortsater H, Fakhrai-Rad H, Galli J, Luthman H, Bergsten P. Phenotyping of individual pancreatic islets locates genetic defects in stimulus secretion coupling to Niddm1i within the major diabetes locus in GK rats. Diabetes 50: 2737-2743, 2001.
43. Manning AK, Hivert MF, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H, Rybin D, Liu CT, Bielak LF, Prokopenko I, Amin N, Barnes D, Cadby G, Hottenga JJ, Ingelsson E, Jackson AU, Johnson T, Kanoni S, Ladenvall C, Lagou V, Lahti J, Lecoeur C, Liu Y, Martinez-Larrad MT, Montasser ME, Navarro P, Perry JR, Rasmussen-Torvik LJ, Salo P, Sattar N, Shungin D, Strawbridge RJ, Tanaka T, van Duijn CM, An P, de Andrade M, Andrews JS, Aspelund T, Atalay M, Aulchenko Y, Balkau B, Bandinelli S, Beckmann JS, Beilby JP, Bellis C, Bergman RN, Blangero J, Boban M, Boehnke M, Boerwinkle E, Bonnycastle LL, Boomsma DI, Borecki IB, Bottcher Y, Bouchard C, Brunner E, Budimir D, Campbell H, Carlson O, Chines PS, Clarke R, Collins FS, Corbaton-Anchuelo A, Couper D, de Faire U, Dedoussis GV, Deloukas P, Dimitriou M, Egan JM, Eiriksdottir G, Erdos MR, Eriksson JG, Eury E, Ferrucci L, Ford I, Forouhi NG, Fox CS, Franzosi MG, Franks PW, Frayling TM, Froguel P, Galan P, de Geus E, Gigante B, Glazer NL, Goel A, Groop L, Gudnason V, Hallmans G, Hamsten A, Hansson O, Harris TB, Hayward C, Heath S, Hercberg S, Hicks AA, Hingorani A, Hofman A, Hui J, Hung J, et al. A genomewide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet 44: 659-660, 2012.
44. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and betacell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412-419, 1985.
45. McCulloch C, Neuhaus J, Searle SR. Generalized, Linear, and Mixed Models. Hoboken: Wiley, 2008.
46. Meigs JB, Wilson PW, Fox CS, Vasan RS, Nathan DM, Sullivan LM, D'Agostino RB. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab 91: 2906-2912, 2006.
47. Moreno C, Kennedy K, Andrae JW, Jacob HJ. Genome-wide scanning with SSLPs in the rat. Methods Mol Med 108: 131-138, 2005.
48. Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab 297: E1247-E1259, 2009.
49. Mott R, Talbot CJ, Turri MG, Collins AC, Flint J. A method for fine mapping quantitative trait loci in outbred animal stocks. Proc Natl Acad Sci USA 97: 12649-12654, 2000.
50. Muoio DM, Newgard CB. Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 9: 193-205, 2008.
51. Nguyen QM, Srinivasan SR, Xu JH, Chen W, Berenson GS. Fasting plasma glucose levels within the normoglycemic range in childhood as a predictor of prediabetes and type 2 diabetes in adulthood: the Bogalusa Heart Study. Arch Pediatr Adolesc Med 164: 124-128, 2010.
52. Nichols GA, Hillier TA, Brown JB. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis. Am J Med 121: 519-524, 2008.
53. Nobrega MA, Woods LC, Fleming S, Jacob HJ. Distinct genetic regulation of progression of diabetes and renal disease in the Goto-Kakizaki rat. Physiol Genomics 39: 38-46, 2009.
54. Parker CC, Sokoloff G, Cheng R, Palmer AA. Genome-wide association for fear conditioning in an advanced intercross mouse line. Behav Genet 42: 437-448, 2012.
55. Phillips DI, Clark PM, Hales CN, Osmond C. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med 11: 286-292, 1994.
56. Pinheiro J, Bates D. Mixed Effects Models in S and S-Plus. New York: Springer, 2000.
57. Polonsky KS, Sturis J, Bell GI. Seminars in Medicine of the Beth Israel Hospital, Boston. Non-insulin-dependent diabetes mellitus-a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med 334: 777-783, 1996.
58. R Development Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria, 2012.
59. Reaven GM. Insulin resistance: the link between obesity and cardiovascular disease. Med Clin North Am 95: 875-892, 2011.
60. Ronnegard L, Valdar W. Detecting major genetic loci controlling phenotypic variability in experimental crosses. Genetics 188: 435-447, 2011.
61. Samocha KE, Lim JE, Cheng R, Sokoloff G, Palmer AA. Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F(2) and advanced intercross lines. Genes Brain Behav 9: 759-767, 2010.
62. Saxena R, Elbers CC, Guo Y, Peter I, Gaunt TR, Mega JL, Lanktree MB, Tare A, Castillo BA, Li YR, Johnson T, Bruinenberg M, Gilbert-Diamond D, Rajagopalan R, Voight BF, Balasubramanyam A, Barnard J, Bauer F, Baumert J, Bhangale T, Bohm BO, Braund PS, Burton PR, Chandrupatla HR, Clarke R, Cooper-DeHoff RM, Crook ED, Davey-Smith G, Day IN, de Boer A, de Groot MC, Drenos F, Ferguson J, Fox CS, Furlong CE, Gibson Q, Gieger C, Gilhuijs-Pederson LA, Glessner JT, Goel A, Gong Y, Grant SF, Grobbee DE, Hastie C, Humphries SE, Kim CE, Kivimaki M, Kleber M, Meisinger C, Kumari M, Langaee TY, Lawlor DA, Li M, Lobmeyer MT, Maitland-van der Zee AH, Meijs MF, Molony CM, Morrow DA, Murugesan G, Musani SK, Nelson CP, Newhouse SJ, O'Connell JR, Padmanabhan S, Palmen J, Patel SR, Pepine CJ, Pettinger M, Price TS, Rafelt S, Ranchalis J, Rasheed A, Rosenthal E, Ruczinski I, Shah S, Shen H, Silbernagel G, Smith EN, Spijkerman AW, Stanton A, Steffes MW, Thorand B, Trip M, van der Harst P, van der AD, van Iperen EP, van Setten J, van Vliet-Ostaptchouk JV, Verweij N, Wolffenbuttel BH, Young T, Zafarmand MH, Zmuda JM, Boehnke M, Altshuler D, McCarthy M, Kao WH, Pankow JS, Cappola TP, Sever P, Poulter N, Caulfield M, Dominiczak A, Shields DC, Bhatt DL, Zhang L, Curtis SP, Danesh J, Casas JP, van der Schouw YT, Onland-Moret NC, Doevendans PA, Dorn GW 2nd, Farrall M, FitzGerald GA, Hamsten A, Hegele R, Hingorani AD, Hofker MH, Huggins GS, Illig T, Jarvik GP, Johnson JA, Klungel OH, Knowler WC, Koenig W, März W, Meigs JB, Melander O, Munroe PB, Mitchell BD, Bielinski SJ, Rader DJ, Reilly MP, Rich SS, Rotter JI, Saleheen D, Samani NJ, Schadt EE, Shuldiner AR, Silverstein R, Kottke-Marchant K, Talmud PJ, Watkins H, Asselbergs FW, de Bakker PI, McCaffery J, Wijmenga C, Sabatine MS, Wilson JG, Reiner A, Bowden DW, Hakonarson H, Siscovick DS, Keating BJ. Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci. Am J Hum Genet 90: 410-425, 2012.
63. Solberg Woods LC, Ahmadiyeh N, Baum A, Shimomura K, Li Q, Steiner DF, Turek FW, Takahashi JS, Churchill GA, Redei EE. Identification of genetic loci involved in diabetes using a rat model of depression. Mamm Genome 20: 486-497, 2009.
64. Solberg Woods LC, Holl K, Tschannen M, Valdar W. Fine-mapping a locus for glucose tolerance using heterogeneous stock rats. Physiol Genomics 41: 102-108, 2010.
65. Stephenson AG. evd: extreme value distributions. RNews 2: 31-32, 2002.
66. Strawbridge RJ, Dupuis J, Prokopenko I, Barker A, Ahlqvist E, Rybin D, Petrie JR, Travers ME, Bouatia-Naji N, Dimas AS, Nica A, Wheeler E, Chen H, Voight BF, Taneera J, Kanoni S, Peden JF, Turrini F, Gustafsson S, Zabena C, Almgren P, Barker DJ, Barnes D, Dennison EM, Eriksson JG, Eriksson P, Eury E, Folkersen L, Fox CS, Frayling TM, Goel A, Gu HF, Horikoshi M, Isomaa B, Jackson AU, Jameson KA, Kajantie E, Kerr-Conte J, Kuulasmaa T, Kuusisto J, Loos RJ, Luan J, Makrilakis K, Manning AK, Martinez-Larrad MT, Narisu N, Nastase Mannila M, Ohrvik J, Osmond C, Pascoe L, Payne F, Sayer AA, Sennblad B, Silveira A, Stancakova A, Stirrups K, Swift AJ, Syvanen AC, Tuomi T, van't Hooft FM, Walker M, Weedon MN, Xie W, Zethelius B, Ongen H, Malarstig A, Hopewell JC, Saleheen D, Chambers J, Parish S, Danesh J, Kooner J, Ostenson CG, Lind L, Cooper CC, Serrano-Rios M, Ferrannini E, Forsen TJ, Clarke R, Franzosi MG, Seedorf U, Watkins H, Froguel P, Johnson P, Deloukas P, Collins FS, Laakso M, Dermitzakis ET, Boehnke M, McCarthy MI, Wareham NJ, Groop L, Pattou F, Gloyn AL, Dedoussis GV, Lyssenko V, Meigs JB, Barroso I, Watanabe RM, Ingelsson E, et al. Genomewide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes 60: 2624-2634, 2011.
67. Svenson KL, Gatti DM, Valdar W, Welsh CE, Cheng R, Chesler EJ, Palmer AA, McMillan L, Churchill GA. High-resolution genetic mapping using the Mouse Diversity outbred population. Genetics 190: 437-447, 2012.
68. Tan JT, Nurbaya S, Gardner D, Ye S, Tai ES, Ng DP. Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore. Diabetes 58: 1445-1449, 2009.
69. Tura A, Kautzky-Willer A, Pacini G. Insulinogenic indices from insulin and C-peptide: comparison of beta-cell function from OGTT and IVGTT. Diabetes Res Clin Pract 72: 298-301, 2006.
70. Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, Ng DP, Holmkvist J, Borch-Johnsen K, Jorgensen T, Sandbaek A, Lauritzen T, Hansen T, Nurbaya S, Tsunoda T, Kubo M, Babazono T, Hirose H, Hayashi M, Iwamoto Y, Kashiwagi A, Kaku K, Kawamori R, Tai ES, Pedersen O, Kamatani N, Kadowaki T, Kikkawa R, Nakamura Y, Maeda S. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 40: 1098-1102, 2008.
71. Valdar W, Holmes CC, Mott R, Flint J. Mapping in structured populations by resample model averaging. Genetics 182: 1263-1277, 2009.
72. Valdar W, Solberg LC, Gauguier D, Burnett S, Klenerman P, Cookson WO, Taylor MS, Rawlins JN, Mott R, Flint J. Genome-wide genetic association of complex traits in heterogeneous stock mice. Nat Genet 38: 879-887, 2006.
73. Valdar W, Solberg LC, Gauguier D, Cookson WO, Rawlins NJ, Mott R, Flint J. Genetic and environmental effects on complex traits in mice. Genetics 174: 959-984, 2006.
74. van de Bunt M, Gloyn AL. From genetic association to molecular mechanism. Curr Diab Rep 10: 452-466, 2010.
75. van Den Brandt J, Kovacs P, Kloting I. Metabolic variability among disease-resistant inbred rat strains and in comparison with wild rats (Rattus norvegicus). Clin Exp Pharmacol Physiol 27: 793-795, 2000.
76. Venables WN, Ripley BD. Modern Applied Statistics. New York: Springer, 2002.
77. Visscher PM, Thompson R, Haley CS. Confidence intervals in QTL mapping by bootstrapping. Genetics 143: 1013-1020, 1996.
78. 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 Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Bengtsson Bostrom K, 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 Herpt T, 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; MAGIC investigators; GIANT Consortium. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42: 579-589, 2010.
79. Wei S, Wei K, Moralejo DH, Ogino T, Koike G, Jacob HJ, Sugiura K, Sasaki Y, Yamada T, Matsumoto K. Mapping and characterization of quantitative trait loci for non-insulin-dependent diabetes mellitus with an improved genetic map in the Otsuka Long-Evans Tokushima fatty rat. Mamm Genome 10: 249-258, 1999.
80. Yalcin B, Flint J, Mott R. Using progenitor strain information to identify quantitative trait nucleotides in outbred mice. Genetics 171: 673-681, 2005.
81. Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, Hirota Y, Mori H, Jonsson A, Sato Y, Yamagata K, Hinokio Y, Wang HY, Tanahashi T, Nakamura N, Oka Y, Iwasaki N, Iwamoto Y, Yamada Y, Seino Y, Maegawa H, Kashiwagi A, Takeda J, Maeda E, Shin HD, Cho YM, Park KS, Lee HK, Ng MC, Ma RC, So WY, Chan JC, Lyssenko V, Tuomi T, Nilsson P, Groop L, Kamatani N, Sekine A, Nakamura Y, Yamamoto K, Yoshida T, Tokunaga K, Itakura M, Makino H, Nanjo K, Kadowaki T, Kasuga M. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 40: 1092-1097, 2008.
82. Yu W, Hu C, Zhang R, Wang C, Qin W, Lu J, Jiang F, Tang S, Bao Y, Xiang K, Jia W. Effects of KCNQ1 polymorphisms on the therapeutic efficacy of oral antidiabetic drugs in Chinese patients with type 2 diabetes. Clin Pharmacol Ther 89: 437-442, 2011.