Evidence map›Paper›PMID 28905132›Full record

ArticleDiabetologia2017

Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium.

Stephanie A Bien, James S Pankow, Jeffrey Haessler, Yinchang Lu, Nathan Pankratz, Rebecca R Rohde, Alfred Tamuno, Christopher S Carlson, Fredrick R Schumacher, Petra Bůžková and 22 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.

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  7. Genomics and Functional Genomics of Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors at 19 institutions in 2 countries.

Stephanie A BienDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA, 98109-1024, USA. sbien@fredhutch.org.
James S PankowDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
Jeffrey HaesslerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA, 98109-1024, USA.
Yinchang LuDepartment of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Rebecca R RohdeDepartment of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alfred TamunoThe Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Christopher S CarlsonDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA, 98109-1024, USA.
Fredrick R SchumacherDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
Petra BůžkováDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Martha L DaviglusDepartment of Medicine, Institute for Minority Health Research, University of Illinois at Chicago, Chicago, IL, USA.
Unhee LimEpidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Myriam FornageHuman Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
Lindsay Fernandez-RhodesDepartment of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Larissa Avilés-SantaDivision of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Steven BuyskeDepartment of Genetics, Rutgers University, Piscataway, NJ, USA.
Myron D GrossDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Mariaelisa GraffDepartment of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Carmen R IsasiDepartment of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Lewis H KullerDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
JoAnn E MansonDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Tara C MatiseDepartment of Genetics, Rutgers University, Piscataway, NJ, USA.
Ross L PrenticeDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA, 98109-1024, USA.
Lynne R WilkensEpidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Sachiko YoneyamaDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
Ruth J F LoosThe Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Lucia A HindorffNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Loic Le MarchandEpidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Kari E NorthDepartment of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Ulrike PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA, 98109-1024, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA, 98109-1024, USA.
Fred Hutch Cancer Center · USUniversity of North Carolina at Chapel Hill · USUniversity of Minnesota · USIcahn School of Medicine at Mount Sinai · USNational Institutes of Health · USRutgers, The State University of New Jersey · USAlbert Einstein College of Medicine · USCancer Center of Hawaii · USCase Western Reserve University · USHarvard University · USThe University of Texas Health Science Center at Houston · USUniversity of Hawaiʻi at Mānoa · USUniversity of Hawaii Cancer CenterUniversity of Illinois Chicago · USUniversity of Michigan–Ann Arbor · USUniversity of Pittsburgh · USUniversity of Southern California · USUniversity of Washington · USVanderbilt University · US

Funding

University of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI GERTRAUD MASKARINEC · 1996 to 2026
$56.2M
POPULATION STUDIEST32HD007168 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ELIZABETH A FRANKENBERG · 1985 to 2026
$13.8M
A Genome-wide Association Study of Prostate Cancer in African AmericansU01CA136792 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2009 to 2011
$9.4M
Genetic Epidemiology of Causal Variants Across the Life CourseU01HG004803 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NORTH, KARI E. · 2008 to 2012
$9.0M
Diverse ancestry biobank to map biomedical traits and elucidate health disparitieU01HG007417 · NHGRI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI LOOS, RUTH JF · 2013 to 2017
$3.5M
Exonic variants and their relation to complex traits in minorities of the WHIU01HG007376 · NHGRI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2013 to 2017
$3.2M
WOMENS HEALTH INITIATIVE-N01WH22110N01WH022110 · WH · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ROSS, PRENTICE · 1992 to 2006
$1.2M
NCI NIH HHS P30 CA071789NCI NIH HHS U01 CA136792NHGRI NIH HHS U01 HG004803NHGRI NIH HHS U01 HG007376NHGRI NIH HHS U01 HG007417NICHD NIH HHS T32 HD007168WHI NIH HHS N01 WH022110
6 · The paper itself

Abstract

aims/hypothesisElevated levels of fasting glucose and fasting insulin in non-diabetic individuals are markers of dysregulation of glucose metabolism and are strong risk factors for type 2 diabetes. Genome-wide association studies have discovered over 50 SNPs associated with these traits. Most of these loci were discovered in European populations and have not been tested in a well-powered multi-ethnic study. We hypothesised that a large, ancestrally diverse, fine-mapping genetic study of glycaemic traits would identify novel and population-specific associations that were previously undetectable by European-centric studies.

methodsA multiethnic study of up to 26,760 unrelated individuals without diabetes, of predominantly Hispanic/Latino and African ancestries, were genotyped using the Metabochip. Transethnic meta-analysis of racial/ethnic-specific linear regression analyses were performed for fasting glucose and fasting insulin. We attempted to replicate 39 fasting glucose and 17 fasting insulin loci. Genetic fine-mapping was performed through sequential conditional analyses in 15 regions that included both the initially reported SNP association(s) and denser coverage of SNP markers. In addition, Metabochip-wide analyses were performed to discover novel fasting glucose and fasting insulin loci. The most significant SNP associations were further examined using bioinformatic functional annotation.

resultsPreviously reported SNP associations were significantly replicated (p ≤ 0.05) in 31/39 fasting glucose loci and 14/17 fasting insulin loci. Eleven glycaemic trait loci were refined to a smaller list of potentially causal variants through transethnic meta-analysis. Stepwise conditional analysis identified two loci with independent secondary signals (G6PC2-rs477224 and GCK-rs2908290), which had not previously been reported. Population-specific conditional analyses identified an independent signal in G6PC2 tagged by the rare variant rs77719485 in African ancestry. Further Metabochip-wide analysis uncovered one novel fasting insulin locus at SLC17A2-rs75862513. CONCLUSIONS/

interpretationThese findings suggest that while glycaemic trait loci often have generalisable effects across the studied populations, transethnic genetic studies help to prioritise likely functional SNPs, identify novel associations that may be population-specific and in turn have the potential to influence screening efforts or therapeutic discoveries. DATA AVAILABILITY: The summary statistics from each of the ancestry-specific and transethnic (combined ancestry) results can be found under the PAGE study on dbGaP here: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356.v1.p1.

Indexed as

Blood GlucoseDiabetes Mellitus, Type 2FastingFemaleGenome-Wide Association StudyHumansInsulinMalePolymorphism, Single NucleotideWhite PeopleBlood GlucoseInsulinFine-mappingGeneticGlucoseGlycaemicInsulinMultiethnicPageTransethnicType 2 diabetes

Identifiers

PMID28905132
PMCPMC5918310
OpenAlexW2754444492

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.