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Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.

TitleAssociation of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.
Publication TypeJournal Article
Year of Publication2019
AuthorsHuang T, Wang T, Zheng Y, et al.
Corporate AuthorsBIRTH-GENE(BIG) Study Working Group
JournalJAMA Netw Open
Volume2
Issue9
Paginatione1910915
Date Published2019 09 04
ISSN2574-3805
KeywordsAdolescent, Adult, Aged, Asian Continental Ancestry Group, Birth Weight, Blood Glucose, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Far East, Female, Genetic Variation, Glycated Hemoglobin A, Humans, Infant, Newborn, Insulin, Male, Mendelian Randomization Analysis, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Young Adult
Abstract

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.

DOI10.1001/jamanetworkopen.2019.10915
Alternate JournalJAMA Netw Open
PubMed ID31539074
PubMed Central IDPMC6755534
Grant ListMC_UU_00011/1 / MRC_ / Medical Research Council / United Kingdom
MC_UP_A620_1017 / MRC_ / Medical Research Council / United Kingdom
19583 / VAC_ / Versus Arthritis / United Kingdom
RG/14/5/30893 / BHF_ / British Heart Foundation / United Kingdom
U01 CA182913 / CA / NCI NIH HHS / United States
MC_UU_12011/4 / MRC_ / Medical Research Council / United Kingdom