Identifying genetic and environmental risk factors for cleft using genome wide association study data

使用全基因组关联研究数据识别唇裂的遗传和环境风险因素

• 批准号: MR/T002093/1
• 负责人: Sarah Lewis
• 金额: $ 62.91万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT002093%2F1
• 关键词: Identifying; genetic; environmental; risk; factors

The Cleft Collective is a set of studies of over 2500 families from across the UK who are affected by cleft lip/palate, whose long-term goals are to develop effective treatments to reduce the risk of cleft and to improve the physical, functional and emotional wellbeing of people born with a cleft. Since the study was established in 2012, we have built one of the world's largest banks of biological samples from children born with a cleft and their parents, in addition we have secured funding to generate genetic data on this cohort. We represent a cleft study of more than 1000 families collected and recruited in Bonn Germany which has DNA samples but does not currently have funding for genotyping. We are now hoping to take advantage of these impressive endeavours by seeking funding to generate genetic data on the Bonn study and then analyse both studies to identify genetic variants which cause cleft both among children born with a cleft and their mothers. We will also use this information to identify non-genetic (environmental) factors that cause clefts using an analytical technique called Mendelian randomization. An improved understanding of these causes will be vital in helping us to achieve our long-term goals, and it will also provide a valuable resource to other researchers from around the world. Findings from this work will be directly relevant to the large global community of people born with a cleft (approximately 1 in every 650 births), but also to the needs of people affected by craniofacial abnormalities and conditions related to cleft which may have many of the same risk factors.

Cleft Collective是一组针对英国各地2500多个受唇腭裂影响的家庭的研究，他们的长期目标是开发有效的治疗方法，以降低唇裂的风险，并改善天生唇腭裂患者的身体、功能和情感健康。自从这项研究于2012年建立以来，我们已经建立了世界上最大的生物样本库之一，来自出生时患有唇裂的儿童及其父母，此外，我们还获得了资金，以生成关于这一队列的基因数据。我们代表的是一项对德国波恩收集和招募的1000多个家庭进行的裂解研究，该研究拥有DNA样本，但目前没有用于基因分型的资金。我们现在希望利用这些令人印象深刻的努力，通过寻求资金来生成波恩研究的基因数据，然后分析这两项研究，以确定在出生时患有唇裂的儿童及其母亲中都会导致唇裂的基因变异。我们还将利用这些信息，通过一种名为孟德尔随机化的分析技术，识别导致唇裂的非遗传(环境)因素。更好地了解这些原因对于帮助我们实现长期目标至关重要，它也将为来自世界各地的其他研究人员提供宝贵的资源。这项工作的发现将直接与全球巨大的先天性唇裂者群体(大约每650名新生儿中就有1人出生)相关，但也与可能具有许多相同风险因素的头面部畸形和与唇裂症相关的疾病影响的人的需求有关。

项目成果

Sidedness in Unilateral Orofacial Clefts: A Systematic Scoping Review

单侧口面裂的单侧性：系统范围界定审查

• DOI: 10.1177/10556656231221027
• 发表时间: 2023
• 期刊: The Cleft Palate Craniofacial Journal
• 作者: Fell M