Chapter 29 Genetics and Diabetes Copyright © 2016 Elsevier Inc. All rights reserved.

Copyright © 2016 Elsevier Inc. All rights reserved. FIGURE 29.1: Monogenic diabetes genes associated with neonatal diabetes mellitus (transient [TNDM] or permanent [PNDM]) and/or MODY. Copyright © 2016 Elsevier Inc. All rights reserved.

Copyright © 2016 Elsevier Inc. All rights reserved. FIGURE 29.2: Loci associated at genome-wide significance with glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Copyright © 2016 Elsevier Inc. All rights reserved. FIGURE 29.3: Per-allele β-coefficients for glucose and insulin concentrations versus ORs for type 2 diabetes (T2D). Panel (A): fasting glucose concentration versus T2D; panel (B): fasting insulin (FI) concentration versus T2D; panel (C): fasting insulin concentration adjusted for BMI versus T2D; and panel (D): 2-hour glucose versus T2D. From R.A. Scott, V. Lagou, R.P. Welch, et al., Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat. Genet. 44 (2012) 9911005. Copyright © 2016 Elsevier Inc. All rights reserved.

Copyright © 2016 Elsevier Inc. All rights reserved. FIGURE 29.4: A schematic representation of how genetic variants influence fasting glucose concentrations in the normoglycemic population and genetic variants that influence the risk of type 2 diabetes may be observed in different glycemic states. Genes determining the normal variation in fasting glucose levels within the normoglycemic population differ from the genes that influence fasting glucose to rise above the normal level leading to type 2 diabetes. There is a gray zone in between these two extremes where people with glucose concentrations approaching the diabetes range (.7 mmol/L) may be either at the top end of the normal range of physiological glucose that shifts slightly upward with age, or at the bottom end of the pathophysiological range and on their way to diabetes. From N.M. De Silva, T.M. Frayling, Novel biological insights emerging from genetic studies of type 2 diabetes and related metabolic traits, Curr. Opin. Lipidol. 21 (2010) 4450. Copyright © 2016 Elsevier Inc. All rights reserved.

Copyright © 2016 Elsevier Inc. All rights reserved. FIGURE 29.5:Joint effects of conventional risk factors and GRS on risk for type 2 diabetes. Values on bars indicate sample size. Left: Joint effects of body mass index and GRS (adjusted for age and sex) from pooled data for men and women. Right: Joint effects of family history of diabetes and GRS (adjusted for age, sex, and body mass index) from pooled data for men and women. From M.C. Cornelis, L. Qi, C. Zhang, et al., Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry, Ann. Intern. Med. 150 (2009) 541550. Copyright © 2016 Elsevier Inc. All rights reserved.

Copyright © 2016 Elsevier Inc. All rights reserved. FIGURE 29.6: ORs of diabetes risk according to joint association of Western dietary pattern scores (in quartiles; Q) and GRSs. The Ors were adjusted for age, BMI, smoking, alcohol consumption, physical activity, family history of diabetes, and total energy intakes. From L. Qi, M.C. Cornelis, C, Zhang, et al., Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men, Am. J. Clin. Nutr. 89 (2009) 14531458. Copyright © 2016 Elsevier Inc. All rights reserved.