A systems based approach to integrating genetic and longitudinal omics data to support diagnosis and prediction of common chronic disease

一种基于系统的方法，整合遗传和纵向组学数据以支持常见慢性病的诊断和预测

• 批准号: MR/M004422/1
• 负责人: Tim Spector
• 金额: $ 232.71万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM004422%2F1
• 关键词: systems; based; approach; integrating; genetic

New technologies are providing opportunities to measure health and disease in many novel ways. The data produced is complex and hard to decipher even by clinicians and health workers. This proposal will investigate how we can use modern molecular techniques which measure in blood the activity and expression of genes and the signatures of chemical reactions (metabolites) in the cell to help predict early disease. To do this we need to explore how global gene expression and metabolites alter over time and how these longitudinal changes along with other new molecular and genetic techniques (called omics) can be used to explore disease mechanisms and susceptibility in ageing populations. To explore the biology of "omic" variability, and to lay the foundation for the clinical integration of genetic and genomic data, we will investigate the longitudinal relationships of cellular and genomic phenotypes, including global gene expression and metabolites, in 700 twins over 7 years, measured at three time-periods. The study subjects derive from the TwinsUK cohort on whom there is already extensive clinical information and cross-sectional genetic and genomic data. Building on these existing data, and making use of the specific methodological opportunities and advantages afforded by the twin design, we will explore how these genomic traits track and vary over time, determine how such variation relates to underlying genetic variation, and explore the joint contribution of genetic and genomic data to disease risk and onset. We will also explore the potential value of monitoring changes in these and other situations within an integrated personalised medicine framework. We will use and develop new analysis approaches to integrate these complex data sets and suggest which changes might play a role in clinically relevant tratis and disease itself. This study will provide novel insights into disease understanding and stimulate larger-scale efforts to combine modern genetic and genomic data for clinical benefit in the future. These studies will pave the way for individualised medicine.

新技术为以许多新颖的方式衡量健康和疾病提供了机会。产生的数据非常复杂，即使是临床医生和卫生工作者也很难破译。该提案将研究我们如何使用现代分子技术来测量血液中基因的活性和表达以及细胞中化学反应（代谢物）的特征，以帮助预测早期疾病。要做到这一点，我们需要探索全球基因表达和代谢物如何随着时间的推移而改变，以及这些纵向变化如何与其他新的分子和遗传技术（称为组学）沿着用于探索老年人群的疾病机制和易感性。为了探索“组学”变异的生物学，并为遗传和基因组数据的临床整合奠定基础，我们将研究细胞和基因组表型的纵向关系，包括全球基因表达和代谢产物，在700对双胞胎中超过7年，在三个时间段测量。研究受试者来自TwinsUK队列，已经有大量的临床信息和横断面遗传和基因组数据。基于这些现有数据，并利用双胞胎设计提供的特定方法学机会和优势，我们将探索这些基因组特征如何随时间跟踪和变化，确定这种变化如何与潜在的遗传变异相关，并探索遗传和基因组数据对疾病风险和发病的共同贡献。我们还将探索在综合个性化医疗框架内监测这些和其他情况变化的潜在价值。我们将使用和开发新的分析方法来整合这些复杂的数据集，并提出哪些变化可能在临床相关的tratis和疾病本身中发挥作用。这项研究将为疾病的理解提供新的见解，并刺激更大规模的努力，以联合收割机结合现代遗传和基因组数据，为未来的临床利益。这些研究将为个性化医疗铺平道路。

项目成果

Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations.

• DOI: 10.1038/s41598-018-33507-7
• 发表时间: 2018-10-15
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Barrios C;Zierer J;Würtz P;Haller T;Metspalu A;Gieger C;Thorand B;Meisinger C;Waldenberger M;Raitakari O;Lehtimäki T;Otero S;Rodríguez E;Pedro-Botet J;Kähönen M;Ala-Korpela M;Kastenmüller G;Spector TD;Pascual J;Menni C
• 通讯作者: Menni C

Time-dependent genetic effects on gene expression implicate aging processes.

• DOI: 10.1101/gr.207688.116
• 发表时间: 2017-04
• 期刊: Genome research
• 影响因子: 7
• 作者: Bryois J;Buil A;Ferreira PG;Panousis NI;Brown AA;Viñuela A;Planchon A;Bielser D;Small K;Spector T;Dermitzakis ET
• 通讯作者: Dermitzakis ET

Identification of Novel Loci Associated With Hip Shape: A Meta-Analysis of Genomewide Association Studies.

• DOI: 10.1002/jbmr.3605
• 发表时间: 2019-03
• 期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
• 作者: Baird DA;Evans DS;Kamanu FK;Gregory JS;Saunders FR;Giuraniuc CV;Barr RJ;Aspden RM;Jenkins D;Kiel DP;Orwoll ES;Cummings SR;Lane NE;Mullin BH;Williams FM;Richards JB;Wilson SG;Spector TD;Faber BG;Lawlor DA;Grundberg E;Ohlsson C;Pettersson-Kymmer U;Capellini TD;Richard D;Beck TJ;Evans DM;Paternoster L;Karasik D;Tobias JH
• 通讯作者: Tobias JH

Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.

• DOI: 10.1186/s13148-021-01018-4
• 发表时间: 2021-02-16
• 期刊: Clinical epigenetics
• 影响因子: 5.7
• 作者: Christiansen C;Castillo-Fernandez JE;Domingo-Relloso A;Zhao W;El-Sayed Moustafa JS;Tsai PC;Maddock J;Haack K;Cole SA;Kardia SLR;Molokhia M;Suderman M;Power C;Relton C;Wong A;Kuh D;Goodman A;Small KS;Smith JA;Tellez-Plaza M;Navas-Acien A;Ploubidis GB;Hardy R;Bell JT
• 通讯作者: Bell JT

ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals.

• DOI: 10.1161/circgen.117.001758
• 发表时间: 2018-01
• 期刊: Circulation. Genomic and precision medicine
• 作者: Bihlmeyer NA;Brody JA;Smith AV;Warren HR;Lin H;Isaacs A;Liu CT;Marten J;Radmanesh F;Hall LM;Grarup N;Mei H;Müller-Nurasyid M;Huffman JE;Verweij N;Guo X;Yao J;Li-Gao R;van den Berg M;Weiss S;Prins BP;van Setten J;Haessler J;Lyytikäinen LP;Li M;Alonso A;Soliman EZ;Bis JC;Austin T;Chen YI;Psaty BM;Harrris TB;Launer LJ;Padmanabhan S;Dominiczak A;Huang PL;Xie Z;Ellinor PT;Kors JA;Campbell A;Murray AD;Nelson CP;Tobin MD;Bork-Jensen J;Hansen T;Pedersen O;Linneberg A;Sinner MF;Peters A;Waldenberger M;Meitinger T;Perz S;Kolcic I;Rudan I;de Boer RA;van der Meer P;Lin HJ;Taylor KD;de Mutsert R;Trompet S;Jukema JW;Maan AC;Stricker BHC;Rivadeneira F;Uitterlinden A;Völker U;Homuth G;Völzke H;Felix SB;Mangino M;Spector TD;Bots ML;Perez M;Raitakari OT;Kähönen M;Mononen N;Gudnason V;Munroe PB;Lubitz SA;van Duijn CM;Newton-Cheh CH;Hayward C;Rosand J;Samani NJ;Kanters JK;Wilson JG;Kääb S;Polasek O;van der Harst P;Heckbert SR;Rotter JI;Mook-Kanamori DO;Eijgelsheim M;Dörr M;Jamshidi Y;Asselbergs FW;Kooperberg C;Lehtimäki T;Arking DE;Sotoodehnia N
• 通讯作者: Sotoodehnia N