Diabetes Care, Vol 23, Issue 5 595-601, Copyright © 2000 by American Diabetes Association

ARTICLES

Diabetes in the Old Order Amish: characterization and heritability analysis of the Amish Family Diabetes Study

WC Hsueh, BD Mitchell, R Aburomia, T Pollin, H Sakul, M Gelder Ehm, BK Michelsen, MJ Wagner, PL St Jean, WC Knowler, DK Burns, CJ Bell and AR Shuldiner
Southwest Foundation for Biomedical Research, San Antonio, Texas, USA.

OBJECTIVE: The Old Order Amish (OOA) are a genetically well-defined closed Caucasian founder population. The Amish Family Diabetes Study was initiated to identify susceptibility genes for type 2 diabetes. This article describes the genetic epidemiology of type 2 diabetes and related traits in this unique population. RESEARCH DESIGN AND METHODS: The study cohort comprised Amish probands with diabetes who were diagnosed between 35 and 65 years of age and their extended adult family members. We recruited 953 adults who represented 45 multigenerational families. Phenotypic characterization included anthropometry, blood pressure, diabetes status, lipid profile, and leptin levels. RESULTS: The mean age of study participants was 46 years, and the mean BMI was 26.9 kg/m2. Subjects with type 2 diabetes were older, more obese, and had higher insulin levels. The prevalence of diabetes in the OOA was approximately half that of the Caucasian individuals who participated in the Third National Health and Nutrition Examination Survey (95% CI 0.23-0.84). The prevalence of diabetes in the siblings of the diabetic probands was 26.5% compared with a prevalence of 7.0% in spouses (lambdaS = 3.28, 95% CI 1.58-6.80). The heritability of diabetes-related quantitative traits was substantial (13-70% for obesity-related traits, 10-42% for glucose levels, and 11-24% for insulin levels during the oral glucose tolerance test; P = 0.01 to <0.0001). CONCLUSIONS: Type 2 diabetes in the Amish has similar phenotypic features to that of the overall Caucasian population, although the prevalence in the Amish community is lower than that of the Caucasian population. There is significant familial clustering of type 2 diabetes and related traits. This unique family collection will be an excellent resource for investigating the genetic underpinnings of type 2 diabetes.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Kottgen, S.-J. Hwang, E. Rampersaud, J. Coresh, K. E. North, J. S. Pankow, J. B. Meigs, J. C. Florez, A. Parsa, D. Levy, et al. TCF7L2 Variants Associate with CKD Progression and Renal Function in Population-Based Cohorts J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1989 - 1999. [Abstract] [Full Text] [PDF]

				E. Rampersaud, C. M. Damcott, M. Fu, H. Shen, P. McArdle, X. Shi, J. Shelton, J. Yin, Y.-P. C. Chang, S. H. Ott, et al. Identification of Novel Candidate Genes for Type 2 Diabetes From a Genome-Wide Association Scan in the Old Order Amish: Evidence for Replication From Diabetes-Related Quantitative Traits and From Independent Populations Diabetes, December 1, 2007; 56(12): 3053 - 3062. [Abstract] [Full Text] [PDF]

				W.-C. Hsueh, K. D. Silver, T. I. Pollin, C. J. Bell, J. R. O'Connell, B. D. Mitchell, and A. R. Shuldiner A Genome-Wide Linkage Scan of Insulin Level Derived Traits: The Amish Family Diabetes Study Diabetes, October 1, 2007; 56(10): 2643 - 2648. [Abstract] [Full Text] [PDF]

				W. Yang, T. Kelly, and J. He Genetic Epidemiology of Obesity Epidemiol. Rev., June 12, 2007; (2007) mxm004v1. [Abstract] [Full Text] [PDF]

				C. M. de Souza Batista, R.-Z. Yang, M.-J. Lee, N. M. Glynn, D.-Z. Yu, J. Pray, K. Ndubuizu, S. Patil, A. Schwartz, M. Kligman, et al. Omentin Plasma Levels and Gene Expression Are Decreased in Obesity Diabetes, June 1, 2007; 56(6): 1655 - 1661. [Abstract] [Full Text] [PDF]

				M. Fu, M. M. Sabra, C. Damcott, T. I. Pollin, L. Ma, S. Ott, J. C. Shelton, X. Shi, L. Reinhart, J. O'Connell, et al. Evidence That Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) on 1q21 is a Type 2 Diabetes Susceptibility Gene in the Old Order Amish Diabetes, May 1, 2007; 56(5): 1363 - 1368. [Abstract] [Full Text] [PDF]

				C. M. Damcott, T. I. Pollin, L. J. Reinhart, S. H. Ott, H. Shen, K. D. Silver, B. D. Mitchell, and A. R. Shuldiner Polymorphisms in the Transcription Factor 7-Like 2 (TCF7L2) Gene Are Associated With Type 2 Diabetes in the Amish: Replication and Evidence for a Role in Both Insulin Secretion and Insulin Resistance Diabetes, September 1, 2006; 55(9): 2654 - 2659. [Abstract] [Full Text] [PDF]

				N. I. Steinle, T. I. Pollin, J. R. O'Connell, B. D. Mitchell, and A. R. Shuldiner Variants in the Ghrelin Gene Are Associated with Metabolic Syndrome in the Old Order Amish J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6672 - 6677. [Abstract] [Full Text] [PDF]

				C. M. Damcott, S. H. Ott, T. I. Pollin, L. J. Reinhart, J. Wang, J. R. O'Connell, B. D. Mitchell, and A. R. Shuldiner Genetic Variation in Adiponectin Receptor 1 and Adiponectin Receptor 2 Is Associated With Type 2 Diabetes in the Old Order Amish Diabetes, July 1, 2005; 54(7): 2245 - 2250. [Abstract] [Full Text] [PDF]

				T. I. Pollin, K. Tanner, J. R. O'Connell, S. H. Ott, C. M. Damcott, A. R. Shuldiner, J. C. McLenithan, and B. D. Mitchell Linkage of Plasma Adiponectin Levels to 3q27 Explained by Association With Variation in the APM1 Gene Diabetes, January 1, 2005; 54(1): 268 - 274. [Abstract] [Full Text] [PDF]

				M. Fu, C. M. Damcott, M. Sabra, T. I. Pollin, S. H. Ott, J. Wang, M. J. Garant, J. R. O'Connell, B. D. Mitchell, and A. R. Shuldiner Polymorphism in the Calsequestrin 1 (CASQ1) Gene on Chromosome 1q21 Is Associated With Type 2 Diabetes in the Old Order Amish Diabetes, December 1, 2004; 53(12): 3292 - 3299. [Abstract] [Full Text] [PDF]

				C. M. Damcott, N. Hoppman, S. H. Ott, L. J. Reinhart, J. Wang, T. I. Pollin, J. R. O'Connell, B. D. Mitchell, and A. R. Shuldiner Polymorphisms in Both Promoters of Hepatocyte Nuclear Factor 4-{alpha} Are Associated With Type 2 Diabetes in the Amish Diabetes, December 1, 2004; 53(12): 3337 - 3341. [Abstract] [Full Text] [PDF]

				S.-H. H. Juo, H.-F. Lin, T. Rundek, E. A. Sabala, B. Boden-Albala, N. Park, M.-Y. Lan, and R. L. Sacco Genetic and Environmental Contributions to Carotid Intima-Media Thickness and Obesity Phenotypes in the Northern Manhattan Family Study Stroke, October 1, 2004; 35(10): 2243 - 2247. [Abstract] [Full Text] [PDF]

				N. I. Steinle, R. Kazlauskaite, I. G. Imumorin, W.-C. Hsueh, T. I. Pollin, J. R. O'Connell, B. D. Mitchell, and A. R. Shuldiner Variation in the Lamin A/C Gene: Associations With Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1708 - 1713. [Abstract] [Full Text] [PDF]

				S. S. Rich, D. W. Bowden, S. M. Haffner, J. M. Norris, M. F. Saad, B. D. Mitchell, J. I. Rotter, C. D. Langefeld, L. E. Wagenknecht, and R. N. Bergman Identification of Quantitative Trait Loci for Glucose Homeostasis: The Insulin Resistance Atherosclerosis Study (IRAS) Family Study Diabetes, July 1, 2004; 53(7): 1866 - 1875. [Abstract] [Full Text] [PDF]

				K J Stewart Exercise training: can it improve cardiovascular health in patients with type 2 diabetes? Br. J. Sports Med., June 1, 2004; 38(3): 250 - 252. [Full Text] [PDF]

				L. J. Baier and R. L. Hanson Genetic Studies of the Etiology of Type 2 Diabetes in Pima Indians: Hunting for Pieces to a Complicated Puzzle Diabetes, May 1, 2004; 53(5): 1181 - 1186. [Full Text] [PDF]

				M. I. McCarthy Progress in defining the molecular basis of type 2 diabetes mellitus through susceptibility-gene identification Hum. Mol. Genet., April 1, 2004; 13(suppl_1): R33 - R41. [Abstract] [Full Text] [PDF]

				R. N. Bergman, D. J. Zaccaro, R. M. Watanabe, S. M. Haffner, M. F. Saad, J. M. Norris, L. E. Wagenknecht, J. E. Hokanson, J. I. Rotter, and S. S. Rich Minimal Model-Based Insulin Sensitivity Has Greater Heritability and a Different Genetic Basis Than Homeostasis Model Assessment or Fasting Insulin Diabetes, August 1, 2003; 52(8): 2168 - 2174. [Abstract] [Full Text] [PDF]

				E. M. Allen, W.-C. Hsueh, M. M. Sabra, T. I. Pollin, P. W. Ladenson, K. D. Silver, B. D. Mitchell, and A. R. Shuldiner A Genome-Wide Scan for Autoimmune Thyroiditis in the Old Order Amish: Replication of Genetic Linkage on Chromosome 5q11.2-q14.3 J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1292 - 1296. [Abstract] [Full Text] [PDF]

				W.-C. Hsueh, P. L. St. Jean, B. D. Mitchell, T. I. Pollin, W. C. Knowler, M. G. Ehm, C. J. Bell, H. Sakul, M. J. Wagner, D. K. Burns, et al. Genome-Wide and Fine-Mapping Linkage Studies of Type 2 Diabetes and Glucose Traits in the Old Order Amish: Evidence for a New Diabetes Locus on Chromosome 14q11 and Confirmation of a Locus on Chromosome 1q21-q24 Diabetes, February 1, 2003; 52(2): 550 - 557. [Abstract] [Full Text] [PDF]

				N. I Steinle, W.-C. Hsueh, S. Snitker, T. I Pollin, H. Sakul, P. L St Jean, C. J Bell, B. D Mitchell, and A. R Shuldiner Eating behavior in the Old Order Amish: heritability analysis and a genome-wide linkage analysis Am. J. Clinical Nutrition, June 1, 2002; 75(6): 1098 - 1106. [Abstract] [Full Text] [PDF]

				L. E. Wagenknecht, D. W. Bowden, J. J. Carr, C. D. Langefeld, B. I. Freedman, and S. S. Rich Familial Aggregation of Coronary Artery Calcium in Families With Type 2 Diabetes Diabetes, April 1, 2001; 50(4): 861 - 866. [Abstract] [Full Text]

				W.-C. Hsueh, B. D. Mitchell, J. L. Schneider, P. L. St. Jean, T. I. Pollin, M. G. Ehm, M. J. Wagner, D. K. Burns, H. Sakul, C. J. Bell, et al. Genome-Wide Scan of Obesity in the Old Order Amish J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1199 - 1205. [Abstract] [Full Text]