Gene Discovery and Pharmacogenetics of Type 2 Diabetes

Dr. Florez’s research interests lie on the genetic determinants of type 2 diabetes and related metabolic traits, and how these variants may impact disease prediction and therapeutic choices.  Thus his laboratory leads two parallel efforts in gene discovery and pharmacogenetics.  With regard to the former, he is involved in the conduct, analysis and integration of genome-wide association studies for type 2 diabetes and related traits, in the Framingham Heart Study and other international consortia such as MAGIC, GENIE, DIAGRAM and SIGMA.  These and other discoveries can then be applied to a clinical trial such as the Diabetes Prevention Program, where participants at high risk of developing diabetes were randomized to preventive interventions: in this manner, whether diabetes-associated genetic variants influence response to treatment can be assessed.  He is also conducting two pharmacogenetic studies: the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGARMGH) intends to establish whether genetic variation at selected loci influences the acute response to a sulfonylurea, metformin or a glucose load; and the Patients with Hyperglycemia Assessed for Response to Metformin by Genetics (PHARMGen) study is mining the electronic medical record to recruit patients who have failed monotherapy, to examine the genetic determinants for metformin response.


1. Dupuis J*, Langenberg C*, Prokopenko I*, Saxena R*, Soranzo N*, … Boehnke M*, McCarthy MI*, Florez JC* and Barroso I* for the MAGIC investigators.  New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.  Nat Genet 2010;42:105-116. (PMID: 20081858).

2. Jablonski KA, McAteer JB, de Bakker PIW, Franks PW, Pollin TI, Hanson RL, Saxena R, Fowler S, Shuldiner AR, Knowler WC, Altshuler D, Florez JC for the Diabetes Prevention Program Research Group.  Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle interventions in the Diabetes Prevention Program.  Diabetes 2010;59:2672-2681. (PMID: 20682687).

3. Hivert M-F, Jablonski KA, Perreault L, Saxena R, McAteer JB, Franks PW, Hamman RF, Kahn SE, Haffner S, the DIAGRAM Consortium, Meigs JB, Altshuler D, Knowler WC, Florez JC for the Diabetes Prevention Program Research Group.  An updated genetic score based on 34 confirmed type 2 diabetes loci is associated with diabetes incidence and regression to normoglycemia in the Diabetes Prevention Program.  Diabetes 2011;60:1340-1348.  (PMID: 21378175).

4. Strawbridge RJ*, Dupuis J*, Prokopenko I*, Barker A*, Ahlqvist E*, … Langenberg C*, Hamsten A* and Florez JC*.  Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.  Diabetes 2011;60:2624-2634.  (PMID: 21873549).

5. Florez JC, Jablonski KA, Taylor A, Mather K, Horton E, White NH, Barrett-Connor E, Knowler WC, Shuldiner AR, Pollin TI for the Diabetes Prevention Program Research Group.  The C allele of ATM rs11212617 does not associate with metformin response in the Diabetes Prevention Program.  Diabetes Care 2012;35:1864-1867. (PMID: 22751958).

6. Scott RA*, Lagou V*, Welch RP*, …, Florez JC*, Langenberg C*, Ingelsson E*, Prokopenko I*, Barroso I*, for the MAGIC investigators.  Large-scale association study using the Metabochip array reveals new loci influencing glycemic traits and provides insight into the underlying biological pathways.  Nat Genet 2012;44:991-1005. (PMID: 22885924).

7. Williams WW*, Salem RM*, McKnight AJ*, Sandholm N*, …, Florez JC for the GENIE Consortium.  Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy.  Diabetes 2012;61:2187-2194. (PMID: 22721967).

8. Sandholm N*, Salem RM*, McKnight AJ*, Brennan EP*, … Hirschhorn JN*, Godson C*, Florez JC*, Groop PH* and Maxwell AP*.  New susceptibility loci associated with kidney disease in type 1 diabetes. PLoS Genetics 2012;8:e1002921. (PMID: 23028342).

9. The SIGMA Type 2 Diabetes Consortium.  Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico.  Nature 2014;506:97-101.  (PMID: 24390345). PMCID in process

Last Updated on September 29, 2020