Evidence mapPaperPMID 19933169Full record

SynthesisHuman molecular genetics2010

Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes.

John R B Perry, Michael N Weedon, Claudia Langenberg, Anne U Jackson, Valeriya Lyssenko, Thomas Sparsø, Gudmar Thorleifsson, Harald Grallert, Luigi Ferrucci, Marcello Maggio and 49 more

Open access · hybridAbstract readMeta-Analysis
In one paragraph

Synthesis in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 8 pooled it
9.4field-weighted citation impact, top 1% 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

114 citing papers in PubMed, 8 syntheses or guidelines pooled it, 222 citations in OpenAlex.

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54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

59 authors at 20 institutions in 8 countries.

John R B PerryGenetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Magdalen Road, Exeter, UK.
Michael N Weedon
Claudia Langenberg
Anne U Jackson
Valeriya Lyssenko
Thomas Sparsø
Gudmar Thorleifsson
Harald Grallert
Luigi Ferrucci
Marcello Maggio
Giuseppe Paolisso
Mark Walker
Colin N A Palmer
Felicity Payne
Elizabeth Young
Christian Herder
Narisu Narisu
Mario A Morken
Lori L Bonnycastle
Katharine R Owen
Beverley Shields
Beatrice Knight
Amanda Bennett
Christopher J Groves
Aimo Ruokonen
Marjo Riitta Jarvelin
Ewan Pearson
Laura Pascoe
Ele Ferrannini
Stefan R Bornstein
Heather M Stringham
Laura J Scott
Johanna Kuusisto
Peter Nilsson
Malin Neptin
Anette P Gjesing
Charlotta Pisinger
Torsten Lauritzen
Annelli Sandbaek
Mike Sampson
MAGIC
Ele Zeggini
Cecilia M Lindgren
Valgerdur Steinthorsdottir
Unnur Thorsteinsdottir
Torben Hansen
Peter Schwarz
Thomas Illig
Markku Laakso
Kari Stefansson
Andrew D Morris
Leif Groop
Oluf Pedersen
Michael Boehnke
Inês Barroso
Nicholas J Wareham
Andrew T Hattersley
Mark I McCarthy
Timothy M Frayling
deCODE Genetics (Iceland) · ISPeninsula College of Medicine and Dentistry · GBUniversity of Michigan–Ann Arbor · USMalmö University · SENational Human Genome Research Institute · USWellcome Sanger Institute · GBHelmholtz Zentrum München · DEKuopio University Hospital · FIMRC Epidemiology Unit · GBNewcastle University · GBNinewells Hospital · GBOxford Centre for Diabetes, Endocrinology and Metabolism · GBTU Dresden · DEUniversity of Exeter · GBUniversity of Oxford · GBAarhus University · DKAddenbrooke's Hospital · GBChurchill Hospital · GBCS Diagnostics · DEDeutsches Diabetes-Zentrum e.V. · DE

Funding

Nation Center- Integrative Biomedical Informatics(RMI)U54DA021519 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2005 to 2005
$3.8M
Identifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2003 to 2025
$3.6M
Aging pathways polymorphisms in older personsR01AG024233 · UNIVERSITY OF CAMBRIDGE · 2004 to 2005
$782k
Targeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · 2005 to 2005
$425k
GENETIC ANALYSIS OF TYPE II DIABETES IN FINNISH POPULATIONZ01HG000024 · HUMAN GENOME RESEARCH · 1995 to 2005
Department of Health DHCS/07/07/008Intramural NIH HHSMedical Research Council G0000649Medical Research Council G016121Medical Research Council G0600717Medical Research Council G0601261Medical Research Council MC_U106179471NHGRI NIH HHS 1 Z01 HG000024NIA NIH HHS R01 AG24233-0NIDA NIH HHS U54 DA021519NIDDK NIH HHS DK062370NIDDK NIH HHS DK069922NIDDK NIH HHS DK072193Wellcome Trust 076113Wellcome Trust 077016/Z/05/ZWellcome Trust 083270/Z/07/ZWellcome Trust 090532Wellcome Trust GR072960
6 · The paper itself

Abstract

Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 x 10(-5)], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes.

Indexed as

AdultAgedCase-Control StudiesDiabetes Mellitus, Type 2FemaleGonadal Steroid HormonesHumansMaleMiddle AgedPolymorphism, Single NucleotideRisk FactorsSex Hormone-Binding GlobulinGonadal Steroid HormonesSex Hormone-Binding Globulin

Identifiers

PMID19933169
PMCPMC2798726
OpenAlexW2139109527

What Socratic holds

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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 Socratic graph.