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一项纵向双胎出生队列研究方案,旨在揭示生命早期环境与遗传风险因素在健康和疾病中的复杂相互作用:重庆纵向双胎研究(LoTiS)

Protocol for a longitudinal twin birth cohort study to unravel the complex interplay between early-life environmental and genetic risk factors in health and disease: the Chongqing Longitudinal Twin Study (LoTiS).

作者信息

Tong Chao, Wen Li, Xia Yinyin, Leong Pamela, Wang Lan, Fan Xin, Han Ting-Li, Craig Jeffrey M, Baker Philip, Saffery Richard, Qi Hongbo

机构信息

Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China.

出版信息

BMJ Open. 2018 Feb 22;8(2):e017889. doi: 10.1136/bmjopen-2017-017889.

Abstract

INTRODUCTION

Non-communicable diseases (NCD) now represent the major burden of adverse health in most countries. It is clear that much of the risk of such conditions begins very early in life, potentially in utero. Given their complex aetiology, an understanding of the origins of NCD requires an in-depth analysis of the interplay between genetic variation and environment, preferably over time. For decades, twin studies have played a key role in understanding such traits. Their strength lies in the ability to disentangle genetic and environmental factors that contribute to a phenotype. This is done by comparing genetically identical monozygotic (MZ) with dizygotic twins, who share on average 50% of genetic variation, or by comparing MZ twins within a pair. This study aims to determine the relative contributions of genes and environment to early-onset intermediate phenotypes related to later adult onset disease (such as growth and neurodevelopment) and to identify specific biomarkers and time points for emergence of phenotypes from infancy, largely independent of underlying genetic factors.

METHODS/DESIGN: The Chongqing Longitudinal Twin Study () will recruit 300 women pregnant with twins, enriched for MZ pregnancies, with follow-up to 3 years of age. Data collection will be undertaken at key time points in gestation (×3), at delivery and postnatally (×9). Maternal and infant biospecimens including blood, urine, hair, nails and buccal swabs along with measures such as fetal scans and body measurements will be collected. Additional information from questionnaires and medical records includes pregnancy, diet, sociodemographics, maternal stress, and infant growth and neurodevelopment.

ETHICS AND DISSEMINATION

This study has been approved by the Ethics Committee of Chongqing Medical University (record no: 201530) and has been registered with the Chinese Clinical Trial Registry (registry no: ChiCTR-OOC-16008203). Results of the recruitment and all subsequent analyses will be submitted for publication in peer-reviewed journals.

TRIAL REGISTRATION NUMBER

ChiCTR-OOC-16008203; Results.

摘要

引言

非传染性疾病(NCD)目前是大多数国家不良健康状况的主要负担。很明显,这些疾病的许多风险在生命早期就已开始,甚至可能在子宫内就已出现。鉴于其复杂的病因,要了解非传染性疾病的起源,需要深入分析基因变异与环境之间的相互作用,最好是长期进行分析。几十年来,双胞胎研究在理解此类特征方面发挥了关键作用。其优势在于能够区分导致某一表型的遗传和环境因素。这通过将基因完全相同的同卵双胞胎(MZ)与平均共享50%基因变异的异卵双胞胎进行比较,或者通过比较一对同卵双胞胎来实现。本研究旨在确定基因和环境对与成年后期发病疾病相关的早发性中间表型(如生长和神经发育)的相对贡献,并确定从婴儿期开始出现表型的特定生物标志物和时间点,很大程度上独立于潜在的遗传因素。

方法/设计:重庆双胞胎纵向研究将招募300名怀有双胞胎的孕妇,其中同卵双胞胎妊娠比例较高,随访至3岁。数据收集将在妊娠关键时间点(3次)、分娩时和产后(9次)进行。将收集包括血液、尿液、头发、指甲和口腔拭子在内的母婴生物样本,以及诸如胎儿扫描和身体测量等指标。问卷和医疗记录中的其他信息包括妊娠情况、饮食、社会人口统计学、母亲压力以及婴儿生长和神经发育情况。

伦理与传播

本研究已获得重庆医科大学伦理委员会批准(记录编号:201530),并已在中国临床试验注册中心注册(注册号:ChiCTR - OOC - 16008203)。招募结果及所有后续分析结果将提交至同行评审期刊发表。

试验注册号

ChiCTR - OOC - 16008203;结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5be/5855313/223be0748cbd/bmjopen-2017-017889f01.jpg

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