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Association of birth weight with Type 2 diabetes and glycemic traits: A mendelian randomization study.
JAMA net. open 2:e1910915 (2019)
Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures: Type 2 diabetes and glycemic traits. Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2019
HGF-reported in Year
2019
ISSN (print) / ISBN
2574-3805
e-ISSN
2574-3805
Journal
JAMA network open
Quellenangaben
Volume: 2,
Issue: 9,
Article Number: e1910915
Publisher
American Medical Association
Publishing Place
Chicago, Ill.
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
POF-Topic(s)
30202 - Environmental Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504000-008
Scopus ID
85072389497
PubMed ID
31539074
Erfassungsdatum
2019-10-09