Conducting a genome-wide association study (GWAS) in the English Longitudinal Study of Ageing (ELSA): a unique resource for UK social science

在英国老龄化纵向研究 (ELSA) 中进行全基因组关联研究 (GWAS)：英国社会科学的独特资源

• 批准号: ES/K005774/1
• 负责人: Meena Kumari
• 金额: $ 254.85万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=ES%2FK005774%2F1
• 关键词: Conducting; genome; wide; association; study

A number of studies suggest that many economic and social outcomes are 'heritable'. However the actual genetic changes associated with these outcomes are yet to be determined. These questions can be addressed by analysis of large population studies which have detailed phenotypic information. However, there are few studies with detailed phenotype measurements of interest to social science and genome wide scan data. ELSA contains cutting edge social and economic phenotype measurements. Additionally, it has a wide variety of biological and health phenotypes and all the measurements have been made at a number of time points. We propose to examine data from approximately 8000 people from the English Longitudinal Study of Ageing and its DNA repository, the EDNAR, with replication in in ELSA's sister study the Health and Retirement study (HRS) which measures many phenotypes. We will create a dataset of genome wide association scan data for the academic community. An important main aim of the project is to provide support for the academic community to use the resource. We will provide high quality genetic data which can be examined alongside the high quality social and economic data that have already been collected in ELSA. A core agenda of this project is develop a new area of research in the UK. We intend to provide training and support to use the repository. In particular, we will organise a workshop inviting participants who play a leadership role in UK social science. The intention is to support the development of skills and capacity within the social science community to enhance the utility of the resource. Further we will perform two projects to demonstrate the utility of the resource. The first will be to examine whether genome wide data explains variability in measures that have economic and social science interest. Data will be conducted in ELSA and in its sister study, the Health and Retirement Study in the United States. Specifically we will focus on risk behaviour (savings behaviour in the context of income); trust (in the context of neighbourhood characteristics) and leadership. These analyses have the potential to impact science in a number of areas. For example, the potential to understand the genetic contribution to variability in social and economic outcomes and the potential to help us understand the biological pathways that underpin these attitudes, behaviours and preferences. The second project will use genetic markers associated with obesity and well-being to examine the their bi-directional association of obesity. These analyses, which are designed to use whole genome information to help to understand whether obesity is causally associated with poor well-being or vice versa, address two areas of great public health significance, namely the obesity epidemic and psychological well-being. Our findings from both demonstration projects will be disseminated to the academic community and the relevant policy organisations through newsletters, conferences, seminars, policy forums and academic papers.

许多研究表明，许多经济和社会成果是“遗传的”。然而，与这些结果相关的实际遗传变化尚未确定。这些问题可以通过分析具有详细表型信息的大群体研究来解决。然而，很少有研究与社会科学和全基因组扫描数据感兴趣的详细表型测量。艾尔莎包含尖端的社会和经济表型测量。此外，它具有各种各样的生物和健康表型，所有测量都是在多个时间点进行的。我们建议检查来自英国老龄化纵向研究及其DNA库EDNAR的约8000人的数据，并在艾尔莎的姐妹研究健康与退休研究（HRS）中复制，该研究测量了许多表型。我们将为学术界创建一个全基因组关联扫描数据集。该项目的一个重要主要目的是为学术界使用该资源提供支持。我们将提供高质量的基因数据，这些数据可以与艾尔莎已经收集的高质量的社会和经济数据一起进行检查。该项目的核心议程是在英国开发一个新的研究领域。我们打算提供培训和支持，以使用储存库。特别是，我们将组织一个研讨会，邀请谁在英国社会科学发挥领导作用的参与者。目的是支持社会科学界的技能和能力发展，以提高资源的效用。此外，我们将执行两个项目，以证明资源的效用。第一个将是检查全基因组数据是否解释了具有经济和社会科学意义的措施的变异性。数据将在艾尔莎及其姊妹研究美国健康与退休研究中进行。具体而言，我们将重点关注风险行为（收入背景下的储蓄行为）;信任（在邻里特征的背景下）和领导力。这些分析有可能在许多领域影响科学。例如，了解遗传因素对社会和经济结果的可变性的贡献的潜力，以及帮助我们了解这些态度、行为和偏好的生物学途径的潜力。第二个项目将使用与肥胖和幸福感相关的遗传标记来研究肥胖的双向关联。这些分析旨在使用全基因组信息来帮助了解肥胖是否与健康状况差有因果关系，反之亦然，解决了两个具有重大公共卫生意义的领域，即肥胖流行病和心理健康。我们会透过通讯、会议、研讨会、政策论坛和学术论文，向学术界和有关的政策组织公布这两个示范项目的研究结果。

项目成果

Effect of smoking on physical function in older adults: a Mendelian randomisation analysis

• DOI: 10.1136/jech-2021-217572
• 发表时间: 2022-02-10
• 期刊: JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
• 影响因子: 6.3
• 作者: Gaggero, Alessio

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease.

• DOI: 10.1016/j.atherosclerosis.2014.07.038
• 发表时间: 2014-11
• 期刊: Atherosclerosis
• 影响因子: 5.3
• 作者: Holmes MV;Frikke-Schmidt R;Melis D;Luben R;Asselbergs FW;Boer JM;Cooper J;Palmen J;Horvat P;Engmann J;Li KW;Onland-Moret NC;Hofker MH;Kumari M;Keating BJ;Hubacek JA;Adamkova V;Kubinova R;Bobak M;Khaw KT;Nordestgaard BG;Wareham N;Humphries SE;Langenberg C;Tybjaerg-Hansen A;Talmud PJ
• 通讯作者: Talmud PJ

Resource profile and user guide of the Polygenic Index Repository.

• DOI: 10.1038/s41562-021-01119-3
• 发表时间: 2021-12
• 期刊: Nature human behaviour
• 影响因子: 29.9
• 作者: Becker J;Burik CAP;Goldman G;Wang N;Jayashankar H;Bennett M;Belsky DW;Karlsson Linnér R;Ahlskog R;Kleinman A;Hinds DA;23andMe Research Group;Caspi A;Corcoran DL;Moffitt TE;Poulton R;Sugden K;Williams BS;Harris KM;Steptoe A;Ajnakina O;Milani L;Esko T;Iacono WG;McGue M;Magnusson PKE;Mallard TT;Harden KP;Tucker-Drob EM;Herd P;Freese J;Young A;Beauchamp JP;Koellinger PD;Oskarsson S;Johannesson M;Visscher PM;Meyer MN;Laibson D;Cesarini D;Benjamin DJ;Turley P;Okbay A
• 通讯作者: Okbay A

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

• DOI: 10.1038/ng.3014
• 发表时间: 2014-08
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Arking, Dan E.;Pulit, Sara L.;Crotti, Lia;Van der Harst, Pim;Munroe, Patricia B.;Koopmann, Tamara T.;Sotoodehnia, Nona;Rossin, Elizabeth J.;Morley, Michael;Wang, Xinchen;Johnson, Andrew D.;Lundby, Alicia;Gudbjartsson, Daniel F.;Noseworthy, Peter A.;Eijgelsheim, Mark;Bradford, Yuki;Tarasov, Kirill V.;Dorr, Marcus;Miiller-Nurasyid, Martina;Lahtinen, Annukka M.;Nolte, Ilja M.;Smith, Albert Vernon;Bis, Joshua C.;Isaacs, Aaron;Newhouse, Stephen J.;Evans, Daniel S.;Post, Wendy S.;Waggott, Daryl;Lyytikainen, Leo-Pekka;Hicks, Andrew A.;Eisele, Lewin;Ellinghaus, David;Hayward, Caroline;Navarro, Pau;Ulivi, Sheila;Tanaka, Toshiko;Tester, David J.;Chatel, Stephanie;Gustafsson, Stefan;Kumari, Meena;Morris, Richard W.;Naluai, Asa T.;Padmanabhan, Sandosh;Kluttig, Alexander;Strohmer, Bernhard;Panayiotou, Andrie G.;Torres, Maria;Knoflach, Michael;Hubacek, Jaroslav A.;Slowikowski, Kamil;Raychaudhuri, Soumya;Kumar, Runjun D.;Harris, Tamara B.;Launer, Lenore J.;Shuldiner, Alan R.;Alonso, Alvaro;Bader, Joel S.;EhreT, Georg;Huang, Hailiang;Kao, W. H. Linda;Strait, James B.;Macfarlane, Peter W.;Brown, Morris;Caulfield, Mark J.;Samani, Nilesh J.;Kronenberg, Florian;Willeit, Johann;Smith, J. Gustav;Greiser, Karin H.;Schwabedissen, Henriette Meyer Zu;Werdan, Karl;Carella, Massimo;Zelante, Leopoldo;Heckbert, Susan R.;Psaty, Bruce M.;Rotter, Jerome I.;Kolcic, Ivana;Poagek, Ozren;Wright, Alan F.;Griffin, Maura;Daly, Mark J.;Arnar, David O.;Holm, Hilma;Thorsteinsdottir, Unnur;Denny, Joshua C.;Roden, Dan M.;Zuvich, Rebecca L.;Emilsson, Valur;Plump, Andrew S.;Larson, Martin G.;O'Donnell, Christopher J.;Yin, Xiaoyan;Bobboll, Marco;D'Adamo, Adamo P.;Iorio, Annamaria;Sinagra, Gianfranco;Carracedo, Angel;Cummings, Steven R.;Nalls, Michael A.;Jula, Antti;Kontula, Kimmo K.;Marjamaa, Annukka;Oikarinen, Lasse;Perola, Markus;Porthan, Kimmo;Erbe, Raimund;Hoffmann, Per;Jockel, Karl-Heinz;Kalsch, Hagen;Nothen, Markus M.;Den Hoed, Marcel;Loos, Ruth J. F.;Thelle, Dag S.;Gieger, Christian;Meitinger, Thomas;Perz, Siegfried;Peters, Annette;Pruchal, Hanna;Sinner, Moritz F.;Waldenberger, Melanie;De Boer, Rudolf A.;Franke, Lude;Van der Vleuten, Pieter A.;Beckmann, Britt Maria;Martens, Eimo;Bardail, Abdennasser;Hofman, Nynke;Wilde, Arthur A. M.;Behr, Elijah R.;Dalageorgou, Chrysoula;Giudicessi, John R.;Medeiros-Domingo, Argelia;Barc, Julien;Kyndt, Florence;Probst, Vincent;Ghidoni, Alice;Insolia, Roberto;Hamilton, Robert M.;Scherer, Stephen W.;Brandimarto, Jeffrey;Margulies, Kenneth;Moravec, Christine E.;Del Greco, Fabiola;Fuchsberger, Christian;O'Connell, Jeffrey R.;Lee, Wai K.;Watt, Graham C. M.;Campbell, Harry;Wild, Sarah H.;El Mokhtari, Nour E.;Frey, Norbert;Asselbergs, Folkert W.;Leach, Irene Mateo;Navis, Gerjan;Van den Berg, Maarten P.;Van Veldhuisen, Dirk J.;Kellis, Manolis;Krijthe, Bouwe P.;Franco, Oscar H.;Hofman, Albert;Kors, Jan A.;Uitterlinden, Andre G.;Witteman, Jacqueline C. M.;Kedenko, Lyudmyla;Lamina, Claudia;Oostra, Ben A.;Abecasis, Goncalo R.;Lakatta, Edward G.;Mulas, Antonella;Orru, Marco;Schlessinger, David;Uda, Manuela;Markus, Marcello R. P.;Volker, Uwe;Snieder, Harold;Spector, Timothy D.;Arnlov, Johan;Lind, Lars;Sundstrom, Johan;Syvanen, Ann-Christine;Kivimaki, Mika;Kahonen, Mika;Mononen, Nina;Raitakari, I. T.;Viikari, Jorma S.;Adamkova, Vera;Kiech, Stefan;Brion, Maria;Nicolaides, Andrew N.;Paulweber, Bernhard;Haerting, Johannes;Dominiczak, Anna F.;Nyberg, Fredrik;Whincup, Peter H.;Hingorani, Aroon D.;Schott, Jean-Jacques;Bezzina, Connie R.;Ingelsson, Erik;Ferrucci, Luigi;Gaspariniin, Paolo;Wilson, James F.;Rudan, Igor;Franke, Andre;Miihleisen, Thomas W.;Pramstaller, Peter P.;Lehtimaki, Terho J.;Paterson, Andrew D.;Parsa, Afshin;Liu, Yongmei;Van Duijn, Cornelia M.;Siscovick, David S.;Gudnason, Vilmundur;Jamshidi, Yalda;Salomaa, Veikko;Felix, Stephan B.;Sanna, Serena;Ritchie, Marylyn D.;Stricker, Bruno H.;Stefansson, Karl;Boyer, Laurie A.;Cappola, Thomas P.;Olsen, Jesper V.;Lage, Kasper;Schwartz, Peter J.;Kaab, Stefan;Chakravarti, Aravinda;Ackerman, Michael J.;Pfeufer, Arne;De Bakker, Paul I. W.;Newton-Cheh, Christopher
• 通讯作者: Newton-Cheh, Christopher

The long-term effects of a polygenetic predisposition to general cognition on healthy cognitive ageing: evidence from the English Longitudinal Study of Ageing.

• DOI: 10.1017/s0033291721004827
• 发表时间: 2023-05
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Ajnakina, Olesya;Murray, Robin;Steptoe, Andrew;Cadar, Dorina
• 通讯作者: Cadar, Dorina