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Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes.
Hum. Mol. Genet. 19, 535-544 (2010)
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DOI
PMC
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.
Impact Factor
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Times Cited
Times Cited
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7.386
2.140
136
137
Anmerkungen
Besondere Publikation
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
GENOME-WIDE ASSOCIATION; AUGSBURG CASE-COHORT; MENDELIAN RANDOMIZATION; INSULIN SENSITIVITY; PROSTATE-CANCER; TESTOSTERONE TREATMENT; POSTMENOPAUSAL WOMEN; SERUM CONCENTRATIONS; STEROID-HORMONES; BODY-COMPOSITION
Sprache
Veröffentlichungsjahr
2010
HGF-Berichtsjahr
2010
ISSN (print) / ISBN
0964-6906
e-ISSN
1460-2083
Zeitschrift
Human Molecular Genetics
Quellenangaben
Band: 19,
Heft: 3,
Seiten: 535-544
Verlag
Oxford University Press
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-503900-003
WOS ID
WOS:000273227200013
Scopus ID
77949911881
PubMed ID
19933169
Erfassungsdatum
2010-03-30