ArticleDiabetes2015
Genetic Variants Associated With Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium.
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In one paragraph
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 6 of them syntheses that pooled it.
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60citing papers in PubMed, 6 pooled it
6.8field-weighted citation impact, top 3% of its field
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 6 syntheses or guidelines pooled it, 85 citations in OpenAlex.
- Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.Nature communications · 2025Pooled it
- Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.Nature genetics · 2023Pooled it
- Identification of genetic effects underlying type 2 diabetes in South Asian and European populations.Communications biology · 2022Pooled it
- A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus.Bioscience reports · 2019Pooled it
- Genome-Wide Association Study Identifies Loci for Liver Enzyme Concentrations in Mexican Americans: The GUARDIAN Consortium.Obesity (Silver Spring, Md.) · 2019Pooled it
- Pooled it
- Neuronal surface P antigen (NSPA) as a novel regulator of energy homeostasis and adipose tissue metabolism.Molecular medicine (Cambridge, Mass.) · 2026Article
- MENTSH: A novel mitochondrial microprotein linked to a SNP associated with type 2 diabetes.Theranostics · 2026Article
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- Mutational signature analyses in multi-child families reveal sources of age-related increases in human germline mutations.Communications biology · 2024Article
- Olanzapine Modulate Lipid Metabolism and Adipose Tissue Accumulation via Hepatic Muscarinic M3 Receptor-Mediated Alk-Related Signaling.Biomedicines · 2024Article
- TheFrontiers in endocrinology · 2024Article
- The melatonin receptor 1B gene links circadian rhythms and type 2 diabetes mellitus: an evolutionary story.Annals of medicine · 2023Review
- Genetic risk prediction in Hispanics/Latinos: milestones, challenges, and social-ethical considerations.Journal of community genetics · 2023Review
- Soluble T-cadherin promotes pancreatic β-cell proliferation by upregulating Notch signaling.iScience · 2022Article
- Celebrities in the heart, strangers in the pancreatic beta cell: Voltage-gated potassium channels KActa physiologica (Oxford, England) · 2022Review
- Population-based genetic effects for developmental stuttering.HGG advances · 2022Article
- Membrane Melatonin Receptors Activated Cell Signaling in Physiology and Disease.International journal of molecular sciences · 2021Review
- Identification of genetic variants for blood insulin level in sex-stratified Korean population and evaluation of the causal relationship between blood insulin level and polycystic ovary syndrome.Genes & genomics · 2021Article
Corrections and comments
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Authors and funding
49 authors at 20 institutions in 2 countries.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC.
Mark O GoodarziDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Carl D LangefeldCenter for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Nan WangDepartment of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA Diabetes & Obesity Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA.
Xiuqing GuoInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA.
Kent D TaylorInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA.
Tasha E FingerlinDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, CO.
Jill M NorrisDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO.
Thomas A BuchananDiabetes & Obesity Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA Department of Physiology and Biophysics, Keck School of Medicine of University of Southern California, Los Angeles, CA Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA.
Anny H XiangResearch and Evaluation Branch, Kaiser Permanente of Southern California, Pasadena, CA.
Talin HarituniansMedical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Julie T ZieglerCenter for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Adrienne H WilliamsCenter for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Darko StefanovskiMedical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Jinrui CuiMedical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Adrienne W MackayDepartment of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA.
Leora F HenkinCenter for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Richard N BergmanCedars-Sinai Diabetes & Obesity Research Institute, Los Angeles, CA.
Xiaoyi GaoDepartment of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA Department of Ophthalmology and Visual Science, University of Illinois at Chicago, Chicago, IL.
James GaudermanDepartment of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA Department of Ophthalmology and Visual Science, University of Illinois at Chicago, Chicago, IL.
Rohit VarmaDepartment of Ophthalmology and Visual Science, University of Illinois at Chicago, Chicago, IL.
Craig L HanisHuman Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, TX.
Nancy J CoxDepartment of Human Genetics, University of Chicago, Chicago, IL.
Heather M HighlandHuman Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, TX.
Jennifer E BelowHuman Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, TX.
Amy L WilliamsProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA Howard Hughes Medical Institute, Chicago, IL Biological Sciences Department, Columbia University, New York, NY.
Noel P BurttProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA.
Carlos A Aguilar-SalinasEndocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Alicia Huerta-ChagoyaEndocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico Universidad Nacional Autónoma de México, Mexico City, Mexico.
Clicerio Gonzalez-VillalpandoCentro de Estudios en Diabetes, Instituto Nacional de Salud Pública, Mexico City, Mexico.
Lorena OrozcoInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA.
Michael Y TsaiDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN.
W Craig JohnsonCollaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Seattle, WA.
Jie YaoInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA.
Laura Rasmussen-TorvikDivision of Epidemiology, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Evanston, IL.
James PankowDivision of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN.
Beverly SnivelyDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Rebecca D JacksonOhio State University Medical Center, Columbus, OH.
Simin LiuDepartment of Epidemiology, Brown University, Providence, RI.
Jerry L NadlerDepartment of Medicine, Eastern Virginia Medical School, Norfolk, VA.
Fouad KandeelDepartment of Diabetes, Endocrinology & Metabolism, City of Hope, Duarte, CA.
Yii-Der I ChenInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA.
Donald W BowdenDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC Section on Endocrinology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
Stephen S RichCenter for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA.
Leslie J RaffelMedical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA jrotter@labiomed.org.
Richard M WatanabeDepartment of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA Diabetes & Obesity Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA Department of Physiology and Biophysics, Keck School of Medicine of University of Southern California, Los Angeles, CA rwatanab@usc.edu.
Lynne E WagenknechtCenter for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC lwgnkcht@wakehealth.edu.
Wake Forest University · USCedars-Sinai Medical Center · USUniversity of Southern California · USThe University of Texas Health Science Center at Houston · USUniversity of California, Los Angeles · USBroad Institute · USInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXUniversity of Illinois Chicago · USBrown University · USCity of Hope · USColorado School of Public Health · USColumbia University · USEastern Virginia Medical School · USInstituto Nacional de Salud Pública · MXKaiser Permanente · USLos Angeles Medical Center · USNational Institute of Genomic Medicine · MXNorthwestern University · USOffice of Public Health Genomics · USThe Lundquist Institute · US
Funding
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MLOS ANGELES LATINO EYE STUDYU10EY011753 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VARMA, ROHIT · 1998 to 2014
$35.6MROLE OF LIPOXYGENASES IN ATHEROGENESIS IN DIABETES MELLITUSP01HL055798 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HEDRICK, CATHERINE C · 1995 to 2016
$28.4MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MTRANSGENIC COREP60DK020595 · NIDDK · UNIVERSITY OF CHICAGO · PI BELL, GRAEME I · 1985 to 2012
$25.5MPilot and Feasibility ProgramP30DK020595 · NIDDK · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2013 to 2026
$20.9MRe-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2MTranslational Core for Therapeutic and Diagnostic DevelopmentP30EY001792 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI AAKALU, VINAY · 1985 to 2025
$14.8MMulti-Ethnic Study of Atherosclerosis (MESA) StudyR01HL071205 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI ROTTER, JEROME I · 2003 to 2007
$10.4MGenetics of Beta Cell Failure in Mexican AmericansR01DK061628 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A, XIANG, ANNY H · 2003 to 2012
$10.0MNCATS NIH HHS TL1 TR000432NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1-TR-000040NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1-TR-000124NCATS NIH HHS UL1 TR000430NCRR NIH HHS UL1 RR025005NCRR NIH HHS UL1-RR-025005NEI NIH HHS P30 EY001792NEI NIH HHS R01 EY022651NEI NIH HHS U10-EY-001792NEI NIH HHS U10 EY011753NEI NIH HHS U10-EY-011753NEI NIH HHS U10-EY-022651NHLBI NIH HHS HL-047887NHLBI NIH HHS HL-047889NHLBI NIH HHS HL-047890NHLBI NIH HHS HL-055798NHLBI NIH HHS HL-060919NHLBI NIH HHS HL-060944NHLBI NIH HHS HL-061019NHLBI NIH HHS HL-0697974NHLBI NIH HHS HL-088457NHLBI NIH HHS HL-102830NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N01-HC-95159NHLBI NIH HHS N01-HC-95160NHLBI NIH HHS N01-HC-95161NHLBI NIH HHS N01-HC-95162NHLBI NIH HHS N01-HC-95163NHLBI NIH HHS N01-HC-95164NHLBI NIH HHS N01-HC-95165NHLBI NIH HHS N01-HC-95166NHLBI NIH HHS N01-HC-95167NHLBI NIH HHS N01-HC-95168NHLBI NIH HHS N01-HC-95169NHLBI NIH HHS N02-HL-64278NHLBI NIH HHS P01 HL055798NHLBI NIH HHS R01-HL-025005NHLBI NIH HHS R01 HL060919NHLBI NIH HHS R01 HL060944NHLBI NIH HHS R01 HL061019NHLBI NIH HHS R01 HL071051NHLBI NIH HHS R01-HL-071051NHLBI NIH HHS R01 HL071205NHLBI NIH HHS R01-HL-071205NHLBI NIH HHS R01 HL071250NHLBI NIH HHS R01-HL-071250NHLBI NIH HHS R01 HL071251NHLBI NIH HHS R01-HL-071251NHLBI NIH HHS R01 HL071252NHLBI NIH HHS R01-HL-071252NHLBI NIH HHS R01 HL071258NHLBI NIH HHS R01-HL-071258NHLBI NIH HHS R01 HL071259NHLBI NIH HHS R01-HL-071259NHLBI NIH HHS R01 HL088457NHLBI NIH HHS R01 HL102830NHLBI NIH HHS U01 HL047902NIDDK NIH HHS DK-020595NIDDK NIH HHS DK-061628NIDDK NIH HHS DK-063491NIDDK NIH HHS DK-073541NIDDK NIH HHS DK-079888NIDDK NIH HHS DK-085501NIDDK NIH HHS P30 DK020595NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P60 DK020595NIDDK NIH HHS R01 DK061628NIDDK NIH HHS R01 DK073541NIDDK NIH HHS R01 DK079888NIDDK NIH HHS R01 DK085175NIDDK NIH HHS U01 DK085501
Abstract
Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D.
Indexed as
Genetic VariationBlood GlucoseDatabases, FactualDiabetes Mellitus, Type 2Gene Expression RegulationGenomeGenome-Wide Association StudyGenotypeHispanic or LatinoHomeostasisHumansBlood Glucose
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