Richard M Watanabe, PhD

I have a primary interest in the pathophysiology and genetics of type 2 diabetes mellitus. My research program focuses on genetics, pathophysiology (and the correlation with genetics), and mathematical modeling of physiologic systems.In the area of complex disease genetics, I am focusing on both positional cloning of susceptibility genes for type 2 diabetes and diabetes-related traits and understanding the gene-phenotype relationships and how they are impacted by environmental exposures.

• Polygenic prediction of body mass index and obesity through the life course and across ancestries. Nat Med. 2025 Sep; 31(9):3151-3168.. View in PubMed
• Effect of Osteocalcin on Insulin Sensitivity, Insulin Secretion, and Beta-cell Compensation in Mexican Americans. J Clin Endocrinol Metab. 2025 Aug 11.. View in PubMed
• What Is Gestational Diabetes-Really? Diabetes. 2025 Jul 01; 74(7):1037-1046.. View in PubMed
• Genetic Variations in GCKR and PNPLA3 Regulate Metabolic Balance Across the Liver. Diabetes. 2025 Jul 01; 74(7):1300-1309.. View in PubMed
• Associations between perceived stress and cortisol biomarkers in predominantly Latino adolescents. Sci Rep. 2025 Apr 04; 15(1):11572.. View in PubMed
• Associations Between Perceived Stress and Cortisol Biomarkers in Predominantly Latino Adolescents. Res Sq. 2024 Nov 15.. View in PubMed
• Higher Genetic Risk for Type 2 Diabetes Is Associated With a Faster Decline of β-Cell Function in an East Asian Population. Diabetes Care. 2024 Aug 01; 47(8):1386-1394.. View in PubMed
• Mind- and Body-Based Interventions Improve Glycemic Control in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. J Integr Complement Med. 2023 Feb; 29(2):69-79.. View in PubMed
• A saturated map of common genetic variants associated with human height. Nature. 2022 10; 610(7933):704-712.. View in PubMed
• The trans-ancestral genomic architecture of glycemic traits. Nat Genet. 2021 06; 53(6):840-860.. View in PubMed
• Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. Nat Commun. 2021 Feb 08; 12(1):995.. View in PubMed
• Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. Nat Commun. 2021 01 05; 12(1):24.. View in PubMed
• Insulin Action, Glucose Homeostasis and Free Fatty Acid Metabolism: Insights From a Novel Model. Front Endocrinol (Lausanne). 2021; 12:625701.. View in PubMed
• Corrigendum: Insulin Action, Glucose Homeostasis and Free Fatty Acid Metabolism: Insights From a Novel Model. Front Endocrinol (Lausanne). 2021; 12:789390.. View in PubMed
• rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis. J Hepatol. 2021 01; 74(1):20-30.. View in PubMed
• Assessment of soluble epoxide hydrolase activity in vivo: A metabolomic approach. Prostaglandins Other Lipid Mediat. 2020 06; 148:106410.. View in PubMed
• Genome-Wide Association Study Identifies Loci for Liver Enzyme Concentrations in Mexican Americans: The GUARDIAN Consortium. Obesity (Silver Spring). 2019 08; 27(8):1331-1337.. View in PubMed
• A diet high in sugar-sweetened beverage and low in fruits and vegetables is associated with adiposity and a pro-inflammatory adipokine profile. Br J Nutr. 2018 12; 120(11):1230-1239.. View in PubMed
• Exome Sequencing Identifies Genetic Variants Associated with Circulating Lipid Levels in Mexican Americans: The Insulin Resistance Atherosclerosis Family Study (IRASFS). Sci Rep. 2018 04 04; 8(1):5603.. View in PubMed
• Longitudinal Increases in Adiposity Contribute to Worsening Adipokine Profile over Time in Mexican Americans. Obesity (Silver Spring). 2018 04; 26(4):703-712.. View in PubMed
• Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls. Sci Data. 2018 01 23; 5:180002.. View in PubMed
• Physiologic Interpretation of GWAS Signals for Type 2 Diabetes. Methods Mol Biol. 2018; 1706:323-351.. View in PubMed
• Association of weight gain and fifteen adipokines with declining beta-cell function in Mexican Americans. PLoS One. 2018; 13(8):e0201568.. View in PubMed
• Sequence data and association statistics from 12,940 type 2 diabetes cases and controls. Sci Data. 2017 12 19; 4:170179.. View in PubMed
• Postprandial effect to decrease soluble epoxide hydrolase activity: roles of insulin and gut microbiota. J Nutr Biochem. 2017 11; 49:8-14.. View in PubMed
• A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants. Diabetes. 2017 08; 66(8):2296-2309.. View in PubMed
• A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes. 2017 07; 66(7):2019-2032.. View in PubMed
• Plasminogen Activator Inhibitor-1 Predicts Negative Alterations in Whole-Body Insulin Sensitivity in Chronic HIV Infection. AIDS Res Hum Retroviruses. 2017 07; 33(7):723-727.. View in PubMed
• Genetic regulatory signatures underlying islet gene expression and type 2 diabetes. Proc Natl Acad Sci U S A. 2017 02 28; 114(9):2301-2306.. View in PubMed
• The genetic architecture of type 2 diabetes. Nature. 2016 08 04; 536(7614):41-47.. View in PubMed
• Improved Performance of Dynamic Measures of Insulin Response Over Surrogate Indices to Identify Genetic Contributors of Type 2 Diabetes: The GUARDIAN Consortium. Diabetes. 2016 07; 65(7):2072-80.. View in PubMed
• The genetic regulatory signature of type 2 diabetes in human skeletal muscle. Nat Commun. 2016 06 29; 7:11764.. View in PubMed
• Ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans. Diabetes Care. 2016 Apr; 39(4):547-54.. View in PubMed
• An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes. Endocrinology. 2015 Sep; 156(9):3147-56.. View in PubMed
• Genetic Variants Associated With Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium. Diabetes. 2015 May; 64(5):1853-66.. View in PubMed
• Adults with long-duration type 2 diabetes have blunted glycemic and β-cell function improvements after bariatric surgery. Obesity (Silver Spring). 2015 Mar; 23(3):523-6.. View in PubMed
• Variation in PPARG is associated with longitudinal change in insulin resistance in Mexican Americans at risk for type 2 diabetes. J Clin Endocrinol Metab. 2015 Mar; 100(3):1187-95.. View in PubMed
• A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). PLoS One. 2015; 10(11):e0134649.. View in PubMed
• Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus. PLoS Genet. 2015 Jan; 11(1):e1004876.. View in PubMed
• High calorie intake is associated with worsening insulin resistance and β-cell function in Hispanic women after gestational diabetes mellitus. Diabetes Care. 2014 Dec; 37(12):3294-300.. View in PubMed
• Antiretroviral therapy modifies the genetic effect of known type 2 diabetes-associated risk variants in HIV-infected women. AIDS. 2014 Jul 31; 28(12):1815-23.. View in PubMed
• Genetic variation in MTNR1B is associated with gestational diabetes mellitus and contributes only to the absolute level of beta cell compensation in Mexican Americans. Diabetologia. 2014 Jul; 57(7):1391-9.. View in PubMed
• Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes. 2014 Jun; 63(6):2158-71.. View in PubMed
• Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans. Obesity (Silver Spring). 2014 Apr; 22(4):1157-64.. View in PubMed
• Longitudinal changes in insulin sensitivity and beta cell function between women with and without a history of gestational diabetes mellitus. Diabetologia. 2013 Dec; 56(12):2753-60.. View in PubMed
• Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment. Diabetes Care. 2013 Aug; 36(8):2175-82.. View in PubMed
• High-fat diet is associated with obesity-mediated insulin resistance and β-cell dysfunction in Mexican Americans. J Nutr. 2013 Apr; 143(4):479-85.. View in PubMed
• Self-reported physical activity is associated with β-cell function in Mexican American adults. Diabetes Care. 2013 Mar; 36(3):638-44.. View in PubMed
• Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. Nat Genet. 2013 Feb; 45(2):197-201.. View in PubMed
• Metabolic syndrome is linked to chromosome 7q21 and associated with genetic variants in CD36 and GNAT3 in Mexican Americans. Obesity (Silver Spring). 2012 Oct; 20(10):2083-92.. View in PubMed
• Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012 Sep; 44(9):991-1005.. View in PubMed
• A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet. 2012 May 13; 44(6):659-69.. View in PubMed
• No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels. Diabetes. 2012 May; 61(5):1291-6.. View in PubMed
• Estimating hepatic glucokinase activity using a simple model of lactate kinetics. Diabetes Care. 2012 May; 35(5):1015-20.. View in PubMed
• Pancreatic iron and glucose dysregulation in thalassemia major. Am J Hematol. 2012 Feb; 87(2):155-60.. View in PubMed
• A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One. 2012; 7(1):e29202.. View in PubMed
• Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012; 8(3):e1002607.. View in PubMed
• Deterioration in cardiometabolic risk markers in obese women during depot medroxyprogesterone acetate use. Contraception. 2012 Jan; 85(1):36-41.. View in PubMed
• 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 Oct; 60(10):2624-34.. View in PubMed
• Drugs, diabetes and pharmacogenomics: the road to personalized therapy. Pharmacogenomics. 2011 May; 12(5):699-701.. View in PubMed
• A better index of body adiposity. Obesity (Silver Spring). 2011 May; 19(5):1083-9.. View in PubMed
• Inherited destiny? Genetics and gestational diabetes mellitus. Genome Med. 2011 Mar 25; 3(3):18.. View in PubMed
• A principal components-based clustering method to identify variants associated with complex traits. Hum Hered. 2011; 71(1):50-8.. View in PubMed
• Statistical issues in gene association studies. Methods Mol Biol. 2011; 700:17-36.. View in PubMed
• The genetics of insulin resistance: Where’s Waldo? Curr Diab Rep. 2010 Dec; 10(6):476-84.. View in PubMed
• A low-glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans. Am J Clin Nutr. 2010 Dec; 92(6):1359-68.. View in PubMed
• Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010 Nov; 42(11):937-48.. View in PubMed
• Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet. 2010 Nov; 42(11):949-60.. View in PubMed
• Limitations in surrogate measures of insulin resistance. J Clin Endocrinol Metab. 2010 Nov; 95(11):4874-6.. View in PubMed
• Pharmacogenetics of Anti-Diabetes Drugs. Pharmaceuticals (Basel). 2010 Aug 01; 3(8):2610-2646.. View in PubMed
• Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010 Jul; 42(7):579-89.. View in PubMed
• Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans. Diabetes. 2010 May; 59(5):1266-75.. View in PubMed
• Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010 Feb; 42(2):142-8.. View in PubMed
• New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010 Feb; 42(2):105-16.. View in PubMed
• A principal-components-based clustering method to identify multiple variants associated with rheumatoid arthritis and arthritis-related autoantibodies. BMC Proc. 2009 Dec 15; 3 Suppl 7:S129.. View in PubMed
• Additive effects of genetic variation in GCK and G6PC2 on insulin secretion and fasting glucose. Diabetes. 2009 Dec; 58(12):2946-53.. View in PubMed
• Evidence for sex-specific associations between variation in acid phosphatase locus 1 (ACP1) and insulin sensitivity in Mexican-Americans. J Clin Endocrinol Metab. 2009 Oct; 94(10):4094-102.. View in PubMed
• Obesity attenuates the contribution of African admixture to the insulin secretory profile in peripubertal children: a longitudinal analysis. Obesity (Silver Spring). 2009 Jul; 17(7):1318-25.. View in PubMed
• Variation in IGF2BP2 interacts with adiposity to alter insulin sensitivity in Mexican Americans. Obesity (Silver Spring). 2009 Apr; 17(4):729-36.. View in PubMed
• Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009 Jan; 41(1):25-34.. View in PubMed
• Variants in MTNR1B influence fasting glucose levels. Nat Genet. 2009 Jan; 41(1):77-81.. View in PubMed
• Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet. 2009 Jan; 41(1):82-8.. View in PubMed
• OGTT-derived measures of insulin sensitivity are confounded by factors other than insulin sensitivity itself. Obesity (Silver Spring). 2008 Aug; 16(8):1938-45.. View in PubMed
• Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. J Clin Invest. 2008 Jul; 118(7):2620-8.. View in PubMed
• Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008 May; 40(5):638-45.. View in PubMed
• Evidence of interaction between PPARG2 and HNF4A contributing to variation in insulin sensitivity in Mexican Americans. Diabetes. 2008 Apr; 57(4):1048-56.. View in PubMed
• Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet. 2008 Feb; 40(2):198-203.. View in PubMed
• Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008 Feb; 40(2):161-9.. View in PubMed
• Prioritized subset analysis: improving power in genome-wide association studies. Hum Hered. 2008; 65(3):129-41.. View in PubMed
• Variants in the plasmacytoma variant translocation gene (PVT1) are associated with end-stage renal disease attributed to type 1 diabetes. Diabetes. 2007 Dec; 56(12):3027-32.. View in PubMed
• Genetics of gestational diabetes mellitus and type 2 diabetes. Diabetes Care. 2007 Jul; 30 Suppl 2:S134-40.. View in PubMed
• What is gestational diabetes? Diabetes Care. 2007 Jul; 30 Suppl 2:S105-11.. View in PubMed
• Reduction in added sugar intake and improvement in insulin secretion in overweight latina adolescents. Metab Syndr Relat Disord. 2007 Jun; 5(2):183-93.. View in PubMed
• A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007 Jun 01; 316(5829):1341-5.. View in PubMed
• Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes mellitus and interacts with adiposity to alter insulin secretion in Mexican Americans. Diabetes. 2007 May; 56(5):1481-5.. View in PubMed
• Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes. Diabetes. 2007 Jan; 56(1):256-64.. View in PubMed
• Subsets of Finns with high HDL to total cholesterol ratio show evidence for linkage to type 2 diabetes on chromosome 6q. Hum Hered. 2007; 63(1):17-25.. View in PubMed
• Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns. Diabetes. 2006 Sep; 55(9):2534-40.. View in PubMed
• Impact of ABCB1 (MDR1) haplotypes on tacrolimus dosing in adult lung transplant patients who are CYP3A5 *3/*3 non-expressors. Transpl Immunol. 2006 Jan; 15(3):235-40.. View in PubMed
• Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns. Hum Genet. 2005 Nov; 118(2):245-54.. View in PubMed
• Sequence variation in PPARG may underlie differential response to troglitazone. Diabetes. 2005 Nov; 54(11):3319-25.. View in PubMed
• Ordered subset analysis in genetic linkage mapping of complex traits. Genet Epidemiol. 2004 Jul; 27(1):53-63.. View in PubMed
• Acute alcohol consumption improves insulin action without affecting insulin secretion in type 2 diabetic subjects. Diabetes Care. 2004 Jun; 27(6):1369-74.. View in PubMed
• Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator-activated receptor-gamma2 gene variant: results from the Troglitazone in Prevention of Diabetes (TRIPOD) study. Diabetes Care. 2004 Jun; 27(6):1365-8.. View in PubMed
• Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes. 2004 Apr; 53(4):1141-9.. View in PubMed
• A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14. Diabetes. 2004 Mar; 53(3):821-9.. View in PubMed
• Minimal model-based insulin sensitivity has greater heritability and a different genetic basis than homeostasis model assessment or fasting insulin. Diabetes. 2003 Aug; 52(8):2168-74.. View in PubMed
• MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther. 2003; 5(6):1003-15.. View in PubMed
• Insulin resistance and associated compensatory responses in african-american and Hispanic children. Diabetes Care. 2002 Dec; 25(12):2184-90.. View in PubMed
• Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort. Diabetes. 2002 May; 51(5):1644-8.. View in PubMed
• Glucose tolerance during moderate alcohol intake: insights on insulin action from glucose/lactate dynamics. J Clin Endocrinol Metab. 2002 Mar; 87(3):1233-8.. View in PubMed

• Buchanan, Thomas
• Peters, Anne
• Goran, Michael
• Haiman, Christopher
• Page, Kathleen
• Gonzalez, Frank