Data from: Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? a historical cohort study.

Objectives: Famine exposure in utero can ‘programme’ an individual towards type 2 diabetes and obesity in later life. We sought to identify, (i) whether Bangladeshis exposed to famine during developmental life are programmed towards diabetes and obesity, (ii) whether this programming was specific to gestational or postnatal exposure windows, and, (iii) whether epigenetic differences were associated with famine exposure. Design: a historical cohort study was performed, as part of a wider cross-sectional survey. Exposure to famine was defined through birth date and historical records and participants were selected according to: (A) exposure to famine in postnatal life, (B) exposure to famine during gestation, and (C) unexposed. Setting: Matlab, a rural area in the Chittagong division of Bangladesh. Participants: young adult men and women (n=190) recruited to a historical cohort study with a randomised subsample included in an epigenetic study (n=143). Outcome measures: primary outcome measures of weight, body mass index, and oral glucose tolerance tests (0 and 120 minutes glucose). Secondary outcome measures included DNA methylation using genome-wide and targeted analysis of metastable epialleles sensitive to maternal nutrition. Results: More young adults exposed to famine in gestation were underweight than those postnatally-exposed or unexposed. In contrast, more postnatally-exposed were overweight compared to gestationally-exposed or unexposed. Underweight adults exposed to famine in gestation in utero were hyperglycaemic following a glucose tolerance test, and those exposed postnatally had elevated fasting glucose, compared to unexposed. Significant differences in DNA methylation at 7 metastable epialleles (VTRNA2-1, PAX8, PRDM-9, near ZFP57, near BOLA, EXD3) known to vary with gestational famine exposure were identified. Conclusions: Famine exposure in developmental life programmed Bangladeshi offspring towards diabetes and obesity in adulthood but gestational and postnatal windows of exposure had variable effects on phenotype. DNA methylation differences were replicated at previously identified metastable epialleles sensitive to periconceptual famine exposure.研究目的：宫内（in utero）饥荒暴露可对个体产生「程序化编程」效应，使其晚年罹患2型糖尿病（type 2 diabetes）与肥胖的风险显著升高。本研究旨在明确三个核心问题：(i) 孟加拉国人群在发育阶段遭受饥荒暴露后，是否会被程序化导向糖尿病与肥胖；(ii) 此种程序化效应是否特异性对应妊娠期（gestational）或产后（postnatal）暴露窗口；(iii) 表观遗传（epigenetic）差异是否与饥荒暴露相关。 研究设计：本研究为一项历史性队列研究（historical cohort study），隶属于一项更大规模的横断面调查（cross-sectional survey）。饥荒暴露状态通过出生日期与历史档案进行界定，研究对象按以下三类分组：(A) 产后阶段遭受饥荒暴露者，(B) 妊娠期遭受饥荒暴露者，(C) 未遭受饥荒暴露者。 研究场景：孟加拉国吉大港专区的乡村地区马特拉巴（Matlab）。 研究对象：共纳入190名年轻成年男女组成历史性队列，其中随机抽取143个子样本参与表观遗传研究。 结局指标：主要结局指标包括体重、体重指数（body mass index, BMI）以及口服葡萄糖耐量试验（oral glucose tolerance tests, OGTT，0分钟与120分钟血糖值）。次要结局指标包括采用全基因组分析与靶向分析，对受母体营养影响的可变表观等位基因（metastable epialleles）进行DNA甲基化检测。 研究结果：相较于产后暴露组与未暴露组，妊娠期暴露饥荒的年轻成年人中体质量不足者占比更高。与之相反，相较于妊娠期暴露组与未暴露组，产后暴露组中体质量超标者占比更高。与未暴露人群相比，宫内妊娠期饥荒暴露导致体质量不足的成年人在葡萄糖耐量试验后呈现高血糖状态，而产后饥荒暴露人群则表现为空腹血糖（fasting glucose）升高。本研究在7个已被证实与妊娠期饥荒暴露相关的可变表观等位基因（VTRNA2-1、PAX8、PRDM-9、ZFP57邻近区域、BOLA邻近区域、EXD3）处，检测到显著的DNA甲基化差异。 研究结论：发育阶段的饥荒暴露可使孟加拉国子代在成年后罹患糖尿病与肥胖，即出现程序化效应，但妊娠期与产后不同暴露窗口对表型的影响存在差异。本研究在既往已报道的、受围受孕期（periconceptual）饥荒暴露影响的可变表观等位基因处，重复验证了DNA甲基化差异。