Genome-Wide Analyses of Health and Well-Being Phenotypes

健康和福祉表型的全基因组分析

• 批准号: 10263934
• 负责人: Daniel J Benjamin
• 金额: $ 74.75万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10263934
• 关键词: Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Attention deficit hyperactivity disorder; Automobile Driving; Behavioral Genetics; Bioethics; Bioinformatics; Biological; Biological Models; Development; Dietary intake; Early Diagnosis; Early treatment; Epidemiology; Fertility; Funding; Genetic; Genetic Annotation; Genetic Research; Genetic Risk; Genetic study; Genomics; Health; Impaired cognition; Intellectual functioning disability; Joints; Late Onset Alzheimer Disease; Light; Longevity; Medical; Medical Genetics; Methods; Nature; Outcome; Pathway interactions; Patient Self-Report; Personal Satisfaction; Phenotype; Physical activity; Postdoctoral Fellow; Publishing; Research; Research Personnel; Sampling; Schizophrenia; Science of genetics; Social Sciences; Social Work; Sociology; Statistical Methods; Yang; barban; behavioral economics; behavioral outcome; behavioral phenotyping; brain morphology; dalton; depressive neurosis; disorder risk; epidemiology study; experience; gene environment interaction; genetic association; genetic epidemiology; genetic variant; genome wide association study; genome-wide; genome-wide analysis; indexing; interdisciplinary collaboration; method development; mortality; psychogenetics; social science research

Project Summary/Abstract This proposal, “Genome-Wide Analyses of Health and Well-Being Phenotypes,” is a competing renewal for a currently funded, three-year R01. The current R01 is focused on advancing the research of the Social Science Genetic Association Consortium (SSGAC), an interdisciplinary collaboration for conducting large-scale genetic studies of behavioral phenotypes, which is directed by three of the applicants. All of the aims of the R01 were achieved. Its results are being widely used in health and aging-related research in social-science genetics, medical genetics, and epidemiology. This competing renewal proposes to continue the work of the SSGAC. In brief, we propose to: • Conduct genetic-association studies of health and aging-relevant behavioral phenotypes in much larger samples that have now become available. We will complete our study of dietary intake begun under the current R01. In addition, we will undertake large-scale studies of additional phenotypes, including physical activity and self-reported general health. Each of these projects will identify genetic variants associated with the phenotype, analyze biological pathways that underlie these associations, and construct polygenic scores (indexes of many genetic variants) that can have substantial predictive power for the phenotype. • Develop a more powerful method for joint analysis of multiple phenotypes, which will be able to (a) estimate the fraction of genetic variants associated with some set of phenotypes but not others, and (b) identify genetic variants likely to be associated with some set of phenotypes but not others. The results of applying the method will help disentangle different mechanisms by which the genetic variants matter for the phenotypes and will enable the construction of more predictive polygenic scores for each phenotype. • Apply this method to shed light on the shared and unique genetic pathways that influence educational attainment and (late-onset) Alzheimer's disease. This analysis will: (a) identify many new genetic variants associated with Alzheimer's disease; (b) generate more predictive polygenic scores for Alzheimer's disease, facilitating earlier diagnosis and treatment; (c) shed light on hypotheses related to the underlying mechanisms driving the genetic relationship between Alzheimer's disease and educational attainment; and (d) enable biological annotation of genetic variants identified to affect Alzheimer's risk but not educational attainment and which thus may operate through more direct biological pathways on disease risk.

项目摘要/摘要 该建议是“全基因组对健康和福祉表型的分析”，是竞争的续约 目前资助，三年R01。当前的R01专注于推进社会科学的研究 遗传关联财团（SSGAC），用于进行大规模遗传的跨学科合作 行为表型的研究，由三个申请人指导。 R01的所有目的都是 成就了。它的结果广泛用于社会科学遗传学的健康和与衰老有关的研究， 医学遗传学和流行病学。 这项竞争的续约提议继续进行SSGAC的工作。简而言之，我们建议： •在更大的情况下，进行健康和与衰老相关的行为表型的遗传关联研究 现在已可用的样品。我们将完成对饮食摄入的研究 当前R01。此外，我们将对其他表型进行大规模研究，包括物理 活动和自我报告的一般健康。这些项目中的每一个都将确定相关的遗传变异 使用表型，分析这些关联构成的生物途径并构建多基因 分数（许多遗传变异的索引）可以为表型具有实质性的预测能力。 •开发一种更强大的方法来对多种表型进行联合分析，该方法将能够（a） 估计与某些表型相关的遗传变异的比例，而不是其他表型，并且（b） 识别可能与某些表型相关的遗传变异，而不是其他表型相关的。结果 应用该方法将有助于解散遗传变异的不同机制 表型并将为每种表型构建更具预测性的多基因评分。 •将此方法应用于影响教育的共同且独特的遗传途径 成就和（晚期）阿尔茨海默氏病。该分析将：（a）确定许多新的遗传变异 与阿尔茨海默氏病有关； （b）为阿尔茨海默氏病产生更多的预测多基因评分， 促进早期的诊断和治疗； （c）阐明与基础有关的假设 推动阿尔茨海默氏病与教育成果之间遗传关系的机制；和 （d）启用对遗传变异的生物学注释，以影响阿尔茨海默氏症的风险，但不影响教育 成就，因此可以通过更直接的生物学途径进行疾病风险。

项目成果

Wrestling with Public Input on an Ethical Analysis of Scientific Research.

与公众对科学研究伦理分析的意见进行角力。

• DOI: 10.1002/hast.1478
• 发表时间: 2023
• 期刊: The Hastings Center report
• 作者: Martschenko,DaphneOluwaseun;Callier,ShawneequaL;Garrison,Nanibaa'A;Lee,SandraSoo-Jin;Turley,Patrick;Meyer,MichelleN;Parens,Erik
• 通讯作者: Parens,Erik

A General Approach to Adjusting Genetic Studies for Assortative Mating.

调整选型交配遗传研究的一般方法。

• DOI: 10.1101/2023.09.01.555983
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Bilghese,Marta;Manansala,Regina;Jaishankar,Dhruva;Jala,Jonathan;Benjamin,DanielJ;Kimball,Miles;Auer,PaulL;Livermore,MichaelA;Turley,Patrick
• 通讯作者: Turley,Patrick

An epigenome-wide association study meta-analysis of educational attainment.

• DOI: 10.1038/mp.2017.210
• 发表时间: 2017-12
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Karlsson Linnér R;Marioni RE;Rietveld CA;Simpkin AJ;Davies NM;Watanabe K;Armstrong NJ;Auro K;Baumbach C;Bonder MJ;Buchwald J;Fiorito G;Ismail K;Iurato S;Joensuu A;Karell P;Kasela S;Lahti J;McRae AF;Mandaviya PR;Seppälä I;Wang Y;Baglietto L;Binder EB;Harris SE;Hodge AM;Horvath S;Hurme M;Johannesson M;Latvala A;Mather KA;Medland SE;Metspalu A;Milani L;Milne RL;Pattie A;Pedersen NL;Peters A;Polidoro S;Räikkönen K;Severi G;Starr JM;Stolk L;Waldenberger M;Eriksson JG;Esko T;Franke L;Gieger C;Giles GG;Hägg S;Jousilahti P;Kaprio J;Kähönen M;Lehtimäki T;Martin NG;van Meurs JBC;Ollikainen M;Perola M;Posthuma D;Raitakari OT;Sachdev PS;Taskesen E;Uitterlinden AG;Vineis P;Wijmenga C;Wright MJ;Relton C;Davey Smith G;Deary IJ;Koellinger PD;Benjamin DJ
• 通讯作者: Benjamin DJ

Mendelian imputation of parental genotypes improves estimates of direct genetic effects.

• DOI: 10.1038/s41588-022-01085-0
• 发表时间: 2022-06
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Young, Alexander, I;Nehzati, Seyed Moeen;Benonisdottir, Stefania;Okbay, Aysu;Jayashankar, Hariharan;Lee, Chanwook;Cesarini, David;Benjamin, Daniel J.;Turley, Patrick;Kong, Augustine
• 通讯作者: Kong, Augustine

Estimation of indirect genetic effects and heritability under assortative mating.

选型交配下间接遗传效应和遗传力的估计。

• DOI: 10.1101/2023.07.10.548458
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Young,AlexanderStrudwick