Neuroimaging genetics to study social cognitive deficits in ASD and schizophrenia
神经影像遗传学研究自闭症谱系障碍和精神分裂症的社会认知缺陷
基本信息
- 批准号:9131397
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-05-06 至 2020-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAllelesAutistic DisorderAwardBehaviorBehavioralBiologicalBiologyBrainBrain imagingClinicalCognitionCognitiveCognitive deficitsCollectionComorbidityComplexDNADataData SetDevelopmentDiagnosisDiseaseEmpathyEnsureEpidemiologyEtiologyEyeFoundationsFunctional Magnetic Resonance ImagingGenesGeneticGenetic MarkersGenetic Predisposition to DiseaseGenetic RiskGenetic VariationGenetic studyGenomicsGenotypeGoalsHealth BenefitHeritabilityImageIndividualKnowledgeLightMeasuresMedialMeta-AnalysisMethodsMindNational Institute of Mental HealthNeurobiologyNeurodevelopmental DisorderNeurosciencesPathogenicityPathologicPathway interactionsPersonalityPhenotypePreventionPsychiatryPublic HealthReadingResearchResearch Domain CriteriaResearch PriorityResearch Project GrantsResearch TrainingResourcesRestRiskSchizophreniaStatistical Data InterpretationStructureSuggestionSusceptibility GeneTemperamentThickTimeTranscendTranslatingValidity and ReliabilityVariantWorkautism spectrum disorderbasebehavior measurementbrain abnormalitiesburden of illnesscareerclinical applicationcognitive functioncognitive neurosciencecohortdata resourcedesigndisorder riskeffective therapyendophenotypeepidemiology studyevidence baseexome sequencingfunctional disabilitygenetic analysisgenetic variantgenome wide association studygenome-widegenome-wide analysisimaging studyindexinginnovationinsightneural circuitneural correlateneuroimagingneuroimaging markerneuropsychiatric disordernext generation sequencingnovelpost-doctoral trainingpublic health relevancerare variantrelating to nervous systemremediationrisk sharingrisk variantskillssocialsocial cognitiontargeted treatmenttheoriestraittreatment strategy
项目摘要
Recent advances in epidemiologic, brain-imaging, and genomic studies suggest that autism spectrum disorder (ASD) and schizophrenia (SCZ), two of the most heritable and pervasive neurodevelopmental disorders, may share some common etiologic mechanisms. While the two disorders are markedly distinct in terms of developmental trajectories and clinical presentations, it has long been recognized that there is considerable overlap of social cognitive deficits. It is thus a highly plausible yet unanswered question whether this overlap in social cognitive deficits reflects common etiological mechanisms, or represents superficial similarities due to comorbidity or misdiagnosis between these two illnesses. The applicant, Dr. Phil H. Lee proposes to address this research question through integrative neuroimaging genetic studies of ASD and SCZ, starting from genes to neural circuits, and ultimately to behavioral measures of social cognition. Owing to years’ of efforts from worldwide collaborators, Dr. Lee now has access to large-scale genotype data (for genome-wide SNPs, N=32,921; for whole-exome-sequencing data, N=7,000) and an independent neuroimaging cohort of ASD,
SCZ cases and healthy controls for whom a rich set of brain imaging and behavioral measures are available (N=3,752). Using these exceptionally powerful resources, she will investigate predictive relationships between common ASD and SCZ genetic risk burden and brain imaging/behavioral indexes of social cognitive functioning. The successful completion of this study will thus: (1) clarify how genetic variations at multiple levels (i.e., common and rare variants) influence brain structure/function and the development of core social deficits transcending traditional nosologic boundaries; (2) develop novel analytic strategies that are highly innovative and of general applicability to the studies of complex traits; and (3) lay the foundation for the development of biology-based prevention and remediation strategies for this core brain deficit. Dr. Lee’s career goal is to study the etiologic pathways of severe neurodevelopmental disorders, such as autism and schizophrenia, using an integrative analysis of genetic and neuroimaging data. This proposal builds on her postdoctoral training in psychiatric statistical genetics, centered on genome-wide association studies of a variety of neuropsychiatric disorders. While working towards accomplishing the proposed study, Dr. Lee will receive in-depth research training from world’s leading experts in computational genetics, clinical psychiatry, and cognitive neuroscience. This K99 Award will thus provide her with crucial and timely support to develop into an independent translational geneticist, who can effectively design and conduct neuroimaging genetic studies, ensure the validity, reliability and clinical applicability of the research work, and most importantly, is capable of translating the research findings into great public health benefits through the development of evidence-based prevention, diagnosis, and treatment strategies.
流行病学、脑成像和基因组学研究的最新进展表明,自闭症谱系障碍(ASD)和精神分裂症(SCZ)这两种最易遗传和普遍存在的神经发育障碍可能具有共同的病因机制。虽然这两种疾病在发育轨迹和临床表现方面明显不同,但人们很早就认识到,社会认知缺陷存在相当大的重叠。因此,社会认知缺陷的这种重叠是反映了共同的病因机制,还是由于这两种疾病之间的共病或误诊而表现出表面上的相似之处,这是一个非常合理但仍未得到解答的问题。申请者Phil H.Lee博士建议通过对ASD和SCZ的综合神经成像遗传学研究来解决这一研究问题,从基因到神经回路,最终到社会认知的行为测量。由于全球合作者多年来的努力,李博士现在可以获得大规模的基因数据(全基因组SNPs,N=32,921;全外显子组测序数据,N=7,000)和ASD的独立神经成像队列。
SCZ患者和健康对照组,他们有丰富的脑成像和行为测量(N=3,752)。利用这些异常强大的资源,她将调查常见的自闭症和SCZ遗传风险负担与社会认知功能的大脑成像/行为指标之间的预测关系。因此,这项研究的成功完成将:(1)阐明多个水平上的遗传变异(即常见和罕见的变异)如何影响大脑结构/功能和超越传统病因学界限的核心社会缺陷的发展;(2)开发具有高度创新性和普遍适用于复杂特征研究的新的分析策略;以及(3)为开发基于生物学的预防和补救这种核心脑缺陷的策略奠定基础。李博士的职业目标是通过对遗传和神经影像数据的综合分析,研究自闭症和精神分裂症等严重神经发育障碍的病因。这项建议建立在她在精神病学统计遗传学方面的博士后培训基础上,该培训以各种神经精神障碍的全基因组关联研究为中心。在努力完成拟议研究的同时,李博士将接受世界领先的计算遗传学、临床精神病学和认知神经科学专家的深入研究培训。因此,K99奖将为她提供关键和及时的支持,使她发展成为一名独立的翻译遗传学家,能够有效地设计和进行神经成像基因研究,确保研究工作的有效性、可靠性和临床适用性,最重要的是,能够通过制定循证预防、诊断和治疗策略,将研究结果转化为巨大的公共健康利益。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Phil H. Lee其他文献
Genome-wide association study of suicide attempt in psychiatric disorders identifies association with major depression polygenic risk scores
精神疾病自杀企图的全基因组关联研究确定了与重度抑郁症多基因风险评分的关联
- DOI:
10.1101/416008 - 发表时间:
2018 - 期刊:
- 影响因子:0
- 作者:
N. Mullins;T. Bigdeli;A. Børglum;J. Coleman;D. Demontis;A. Fanous;D. Mehta;R. Power;S. Ripke;E. Stahl;A. Starnawska;A. Anjorin;A. Corvin;A. Sanders;A. Forstner;A. Reif;A. Koller;B. Świątkowska;B. Baune;B. Müller;B. Konte;B. Penninx;C. Pato;C. Zai;D. Rujescu;D. Quested;D. Levinson;E. Binder;Enda M. Byrne;E. Agerbo;F. Streit;F. Mayoral;F. Bellivier;F. Degenhardt;G. Breen;G. Morken;G. Turecki;G. Rouleau;H. Grabe;H. Völzke;I. Giegling;I. Agartz;I. Melle;J. Lawrence;J. Potash;J. Walters;J. Strohmaier;Jianxin Shi;J. Hauser;J. Biernacka;J. Vincent;J. Kelsoe;J. Strauss;J. Lissowska;J. Pimm;J. Smoller;J. G. Parra;K. Berger;L. Scott;M. Azevedo;M. Trzaskowski;M. Kogevinas;M. Rietschel;M. Boks;M. Ising;M. Grigoroiu;M. Hamshere;M. Leboyer;M. Frye;M. Nöthen;M. Alda;M. Preisig;M. Nordentoft;M. Boehnke;M. O’Donovan;M. Owen;M. Pato;M. Rentería;M. Budde;M. Weissman;N. Wray;N. Bass;O. Smeland;O. Andreassen;O. Mors;P. Gejman;P. Sklar;P. McGrath;P. Hoffmann;P. McGuffin;Phil H. Lee;R. Kahn;R. Ophoff;R. Adolfsson;S. Auwera;S. Djurovic;Stanley I. Shyn;S. Kloiber;S. Heilmann;S. Jamain;S. Hamilton;S. McElroy;S. Lucae;S. Cichon;T. Schulze;T. Hansen;T. Werge;T. Air;V. Nimgaonkar;V. Appadurai;W. Cahn;Y. Milaneschi;K. Kendler;A. McQuillin;C. Lewis - 通讯作者:
C. Lewis
Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries
颅内和皮质下脑容量的基因组分析产生了多基因评分,解释了不同血统之间的变异
- DOI:
10.1038/s41588-024-01951-z - 发表时间:
2024-10-21 - 期刊:
- 影响因子:29.000
- 作者:
Luis M. García-Marín;Adrian I. Campos;Santiago Diaz-Torres;Jill A. Rabinowitz;Zuriel Ceja;Brittany L. Mitchell;Katrina L. Grasby;Jackson G. Thorp;Ingrid Agartz;Saud Alhusaini;David Ames;Philippe Amouyel;Ole A. Andreassen;Konstantinos Arfanakis;Alejandro Arias-Vasquez;Nicola J. Armstrong;Lavinia Athanasiu;Mark E. Bastin;Alexa S. Beiser;David A. Bennett;Joshua C. Bis;Marco P. M. Boks;Dorret I. Boomsma;Henry Brodaty;Rachel M. Brouwer;Jan K. Buitelaar;Ralph Burkhardt;Wiepke Cahn;Vince D. Calhoun;Owen T. Carmichael;Mallar Chakravarty;Qiang Chen;Christopher R. K. Ching;Sven Cichon;Benedicto Crespo-Facorro;Fabrice Crivello;Anders M. Dale;George Davey Smith;Eco J. C. de Geus;Philip L. De Jager;Greig I. de Zubicaray;Stéphanie Debette;Charles DeCarli;Chantal Depondt;Sylvane Desrivières;Srdjan Djurovic;Stefan Ehrlich;Susanne Erk;Thomas Espeseth;Guillén Fernández;Irina Filippi;Simon E. Fisher;Debra A. Fleischman;Evan Fletcher;Myriam Fornage;Andreas J. Forstner;Clyde Francks;Barbara Franke;Tian Ge;Aaron L. Goldman;Hans J. Grabe;Robert C. Green;Oliver Grimm;Nynke A. Groenewold;Oliver Gruber;Vilmundur Gudnason;Asta K. Håberg;Unn K. Haukvik;Andreas Heinz;Derrek P. Hibar;Saima Hilal;Jayandra J. Himali;Beng-Choon Ho;David F. Hoehn;Pieter J. Hoekstra;Edith Hofer;Wolfgang Hoffmann;Avram J. Holmes;Georg Homuth;Norbert Hosten;M. Kamran Ikram;Jonathan C. Ipser;Clifford R. Jack Jr;Neda Jahanshad;Erik G. Jönsson;Rene S. Kahn;Ryota Kanai;Marieke Klein;Maria J. Knol;Lenore J. Launer;Stephen M. Lawrie;Stephanie Le Hellard;Phil H. Lee;Hervé Lemaître;Shuo Li;David C. M. Liewald;Honghuang Lin;W. T. Longstreth;Oscar L. Lopez;Michelle Luciano;Pauline Maillard;Andre F. Marquand;Nicholas G. Martin;Jean-Luc Martinot;Karen A. Mather;Venkata S. Mattay;Katie L. McMahon;Patrizia Mecocci;Ingrid Melle;Andreas Meyer-Lindenberg;Nazanin Mirza-Schreiber;Yuri Milaneschi;Thomas H. Mosley;Thomas W. Mühleisen;Bertram Müller-Myhsok;Susana Muñoz Maniega;Matthias Nauck;Kwangsik Nho;Wiro J. Niessen;Markus M. Nöthen;Paul A. Nyquist;Jaap Oosterlaan;Massimo Pandolfo;Tomas Paus;Zdenka Pausova;Brenda W. J. H. Penninx;G. Bruce Pike;Bruce M. Psaty;Benno Pütz;Simone Reppermund;Marcella D. Rietschel;Shannon L. Risacher;Nina Romanczuk-Seiferth;Rafael Romero-Garcia;Gennady V. Roshchupkin;Jerome I. Rotter;Perminder S. Sachdev;Philipp G. Sämann;Arvin Saremi;Muralidharan Sargurupremraj;Andrew J. Saykin;Lianne Schmaal;Helena Schmidt;Reinhold Schmidt;Peter R. Schofield;Markus Scholz;Gunter Schumann;Emanuel Schwarz;Li Shen;Jean Shin;Sanjay M. Sisodiya;Albert V. Smith;Jordan W. Smoller;Hilkka S. Soininen;Vidar M. Steen;Dan J. Stein;Jason L. Stein;Sophia I. Thomopoulos;Arthur W. Toga;Diana Tordesillas-Gutiérrez;Julian N. Trollor;Maria C. Valdes-Hernandez;Dennis van ′t Ent;Hans van Bokhoven;Dennis van der Meer;Nic J. A. van der Wee;Javier Vázquez-Bourgon;Dick J. Veltman;Meike W. Vernooij;Arno Villringer;Louis N. Vinke;Henry Völzke;Henrik Walter;Joanna M. Wardlaw;Daniel R. Weinberger;Michael W. Weiner;Wei Wen;Lars T. Westlye;Eric Westman;Tonya White;A. Veronica Witte;Christiane Wolf;Jingyun Yang;Marcel P. Zwiers;M. Arfan Ikram;Sudha Seshadri;Paul M. Thompson;Claudia L. Satizabal;Sarah E. Medland;Miguel E. Rentería - 通讯作者:
Miguel E. Rentería
Title: Analysis of Shared Heritability in Common Disorders of the Brain
标题:常见脑部疾病的共同遗传力分析
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
V. Anttila;B. Bulik;H. Finucane;R. Walters;J. Bras;L. Duncan;V. Escott;G. Falcone;P. Gormley;R. Malik;N. Patsopoulos;S. Ripke;Z. Wei;Phil H. Lee;P. Turley;G. Breen;C. Churchhouse;C. Bulik;M. Daly;S. Faraone;R. Guerreiro;P. Holmans;K. Kendler;B. Koeleman;Alkes Price;J. Scharf;P. Sklar;J. Williams;N. Wood;C. Cotsapas;A. Palotie;J. Smoller;P. Sullivan;J. Rosand;A. Corvin;B. Neale - 通讯作者:
B. Neale
Prioritizing SNPs for Disease-Gene Association Studies: Algorithms and Systems
- DOI:
- 发表时间:
2009-06 - 期刊:
- 影响因子:0
- 作者:
Phil H. Lee - 通讯作者:
Phil H. Lee
Heritability of Neuroanatomical Shape
神经解剖形状的遗传力
- DOI:
10.1101/033407 - 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
T. Ge;M. Reuter;A. Winkler;A. Holmes;Phil H. Lee;Lee S. Tirrell;J. Roffman;R. Buckner;J. Smoller;M. Sabuncu - 通讯作者:
M. Sabuncu
Phil H. Lee的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Phil H. Lee', 18)}}的其他基金
Comprehensive analysis of genetic pleiotropy in eleven neuropsychiatric disorders
11种神经精神疾病遗传多效性综合分析
- 批准号:
9887499 - 财政年份:2019
- 资助金额:
$ 24.9万 - 项目类别:
Comprehensive analysis of genetic pleiotropy in eleven neuropsychiatric disorders
11种神经精神疾病遗传多效性综合分析
- 批准号:
10523102 - 财政年份:2019
- 资助金额:
$ 24.9万 - 项目类别:
Comprehensive analysis of genetic pleiotropy in eleven neuropsychiatric disorders
11种神经精神疾病遗传多效性综合分析
- 批准号:
10292985 - 财政年份:2019
- 资助金额:
$ 24.9万 - 项目类别:
Neuroimaging genetics to study social cognitive deficits in ASD and schizophrenia
神经影像遗传学研究自闭症谱系障碍和精神分裂症的社会认知缺陷
- 批准号:
8846139 - 财政年份:2014
- 资助金额:
$ 24.9万 - 项目类别:
相似海外基金
Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
- 批准号:
502556 - 财政年份:2024
- 资助金额:
$ 24.9万 - 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
- 批准号:
10659303 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
- 批准号:
10674405 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
- 批准号:
10758772 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
- 批准号:
10676499 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
- 批准号:
2748611 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
Studentship
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
- 批准号:
22K05630 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
- 批准号:
10532032 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
- 批准号:
10525070 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
- 批准号:
10689017 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别: