Maternal and Offspring Genetic Risk of Type 2 Diabetes and Offspring Birthweight Among African Ancestry Populations

被引：5

作者：

Rahman, Mohammad L. ^{[1
,3
]}

Shrestha, Deepika ^{[1
]}

Workalemahu, Tsegaselassie ^{[1
]}

Wu, Jing ^{[2
]}

Zhu, Chunming ^{[2
]}

Zhang, Cuilin ^{[1
]}

Tekola-Ayele, Fasil ^{[1
]}

机构：

[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6710B Rockledge Dr,6710B-3204, Bethesda, MD 20892 USA

[2] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA

[3] Harvard Med Sch, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, Boston, MA 02115 USA

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2019年 / 104卷 / 11期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; HYPERGLYCEMIA; INSULIN; OBESITY; GENOTYPE; GLUCOSE; METAANALYSIS; VARIANTS; MELLITUS;

D O I：

10.1210/jc.2018-02756

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives: Maternal genetic risk of type 2 diabetes (T2D) can influence offspring birthweight through shared offspring genetic risk and by altering intrauterine glycemic status. The aim of this study was to estimate the independent effects of maternal and offspring genetic risk scores (GRSs) of T2D on offspring birthweight and the extent to which intrauterine glycemic traits mediate the effect of maternal GRSs on offspring birthweight. Design: The study involved 949 mother-offspring pairs of African ancestry from the Hyperglycemia Adverse Pregnancy Outcome study. GRSs of T2D were calculated separately for mothers and offspring as the weighted sum of 91 T2D risk alleles identified in a genome-wide association study meta-analysis in African Americans. Linear regression models were fit to estimate changes in birthweight by quartiles of GRSs. Mediation analysis was implemented to estimate the direct and indirect effects of maternal GRS on offspring birthweight through cord blood C-peptide and maternal fasting and postchallenge glucose levels. Results: Maternal and offspring GRSs were independently and differentially associated with offspring birthweight. Changes (95% CI) in birthweight across increasing quartiles of maternal GRSs were 0 g (reference), 83.1 g (6.5, 159.6), 103.1 g (26.0, 180.2), and 92.7 g (12.6, 172.8) (P trend = 0.041) and those of offspring GRSs were 0 (reference), -92.0 g (-169.2, -14.9), -64.9 g (-142.4, 12.6), and 2.0 g (-77.8, 81.7) (P trend = 0.032). Cord blood C-peptide mediated the effect of maternal GRS on offspring birthweight, whereas maternal postchallenge glucose levels showed additive effects with maternal GRS on birthweight. Conclusions: Maternal and offspring GRSs of T2D were independently and differentially associated with offspring birthweight.

引用

页码：5032 / 5042

页数：11

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