Latino Ancestry Genomic Psychiatry Cohort

拉丁裔血统基因组精神病学队列

• 批准号: 10455716
• 负责人: Tim Bernard Bigdeli
• 金额: $ 134.04万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10455716
• 关键词: Admixture; African ancestry; Americas; Amerindian; Benchmarking; Bipolar Disorder; Chromosome Mapping; Clinical; Collaborations; Colombian; Complex; Data; Diagnosis; Disease; Enrollment; Equipment and supply inventories; European; European ancestry; Event; Funding; Genetic; Genetic Polymorphism; Genetic Recombination; Genetic Research; Genetic Risk; Genetic Variation; Genome; Genomics; Goals; Haplotypes; Heritability; Human Genetics; Individual; Interview; Joints; Knowledge; Latino; Latino Population; Linkage Disequilibrium; Maps; Medical; Meta-Analysis; Mexican; Minority Groups; National Institute of Mental Health; Outcome; Participant; Patient Self-Report; Patients; Phase; Polygenic Traits; Population; Population Heterogeneity; Psychiatry; Psychoses; Publishing; Questionnaires; Resolution; SNP genotyping; Sampling; Schizophrenia; Signal Transduction; Structure; Variant; ancestry analysis; cognitive testing; cohort; experience; genetic association; genome wide association study; genome-wide; genome-wide analysis; health care disparity; human migration; improved; neuropsychiatry; novel; polygenic risk score; psychiatric genomics; psychiatric symptom; risk variant; screening; statistics; study population; synergism; whole genome

Project Summary The Latino Ancestry-Genomic Psychiatry Cohort (LA-GPC) is an expansion of the GPC into the Latino population. LA and other minority populations have been poorly represented in large-scale genomic studies, and yet these populations (i) suffer the largest disparities in health care and outcomes, and (ii) have the potential to broaden our knowledge of human genetics. In particular, LA genomes are admixed and are characterized by different haplotype blocks than European ancestry (EA) populations. As a consequence, genetic polymorphisms that are in perfect linkage disequilibrium (LD) in Europeans may be broken-up by recombination events in LA genomes, allowing the contributions of different genomic intervals to be assessed independently. Progress to date: The GPC has enrolled and assessed over 5,000 new LA participants and we have recently published a pilot GWAS including both LA and African Ancestry (AA) participants. GWAS meta- analysis of PGC-SCZ2 with pilot results for 4,324 (cases and controls) LA-GPC participants yielded 8 new schizophrenia-associated risk loci, and for 9 loci there was a concomitant reduction in the number of SNPs in the associated interval. Crucially, the resultant cross-ancestry summary statistics, informed by multiple ancestrally diverse cohorts, yielded individual-level polygenic risk scores that explained more variance than analogous scores based on either ancestry alone In Phase 1 of this renewal: we will study genome-wide common variation in our existing LA-GPC and VA- CS#572 combined cohort of 16,124 LA participants. In Phase 2, we will perform an expanded analysis by adding 8,000 new participants ascertained in the LA-GPC, 35,000 additional participants from the VA, 8,000 participants from the NeuroMex study (PI. Koenen), and 10,000 participants from the Colombian study (PI. Freimer). This meta-analysis will include over 77,000 LA participants, a sample of non-Caucasians with the potential for significant novel discovery.

项目摘要 拉丁裔血统基因组精神病学队列（LA-GPC）是GPC向拉丁裔的扩展 人口洛杉矶和其他少数民族人口在大规模基因组研究中的代表性很差， 然而，这些人群（i）在医疗保健和结果方面遭受最大的差异，（ii） 有可能扩大我们对人类遗传学的了解。特别地，LA基因组是混合的， 其特征在于与欧洲血统（EA）群体不同的单倍型块。因此，在这方面， 欧洲人处于完美连锁不平衡（LD）的遗传多态性可能被以下因素打破： LA基因组中的重组事件，允许评估不同基因组间隔的贡献 独立地。 迄今为止的进展：GPC已经招募和评估了5，000多名新的LA参与者， 最近发布了一个试点GWAS，包括LA和非洲制药（AA）参与者。GWAS Meta- 对PGC-SCZ 2与4，324名（病例和对照）LA-GPC参与者的试验结果进行分析，产生了8个新的 精神分裂症相关的风险位点，并为9个位点，有伴随减少的SNP的数量， 相关的间隔。至关重要的是，由此产生的跨祖先汇总统计数据，由多个 祖先不同的队列，产生了个人水平的多基因风险评分，解释了更多的方差， 仅基于任一血统的类似分数 在本次更新的第一阶段：我们将研究我们现有的LA-GPC和VA-1中的全基因组常见变异。 CS#572 16，124名LA受试者的合并队列。在第二阶段，我们将进行扩展分析， 在LA-GPC中增加了8，000名新参与者，VA增加了35，000名参与者， NeuroMex研究的参与者（PI。Koenen）和来自哥伦比亚研究的10，000名参与者（PI。 Freimer）。这项荟萃分析将包括超过77，000名LA参与者，一个非白人样本， 潜在的重大新发现。

项目成果

Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

• DOI: 10.3390/ijms242015339
• 发表时间: 2023-10-19
• 期刊: International journal of molecular sciences
• 影响因子: 5.6

Prognostic value of polygenic risk scores for adults with psychosis.

成人精神病患者多基因风险评分的预后价值。

• DOI: 10.1038/s41591-021-01475-7
• 发表时间: 2021-09
• 期刊: Nature medicine
• 影响因子: 82.9
• 作者: Landi I;Kaji DA;Cotter L;Van Vleck T;Belbin G;Preuss M;Loos RJF;Kenny E;Glicksberg BS;Beckmann ND;O'Reilly P;Schadt EE;Achtyes ED;Buckley PF;Lehrer D;Malaspina DP;McCarroll SA;Rapaport MH;Fanous AH;Pato MT;Pato CN;Bigdeli TB;Nadkarni GN;Charney AW
• 通讯作者: Charney AW

The genomic psychiatry cohort: partners in discovery.

• DOI: 10.1002/ajmg.b.32160
• 发表时间: 2013-06
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
• 影响因子: 2.8
• 作者: Pato, Michele T.;Sobell, Janet L.;Medeiros, Helena;Abbott, Colony;Sklar, Brooke M.;Buckley, Peter F.;Bromet, Evelyn J.;Escamilla, Michael A.;Fanous, Ayman H.;Lehrer, Douglas S.;Macciardi, Fabio;Malaspina, Dolores;McCarroll, Steve A.;Marder, Stephen R.;Moran, Jennifer;Morley, Christopher P.;Nicolini, Humberto;Perkins, Diana O.;Purcell, Shaun M.;Rapaport, Mark H.;Sklar, Pamela;Smoller, Jordan W.;Knowles, James A.;Pato, Carlos N.
• 通讯作者: Pato, Carlos N.

Age at first birth in women is genetically associated with increased risk of schizophrenia.

• DOI: 10.1038/s41598-018-28160-z
• 发表时间: 2018-07-05
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ni G;Gratten J;Wray NR;Lee SH;Schizophrenia Working Group of the Psychiatric Genomics Consortium
• 通讯作者: Schizophrenia Working Group of the Psychiatric Genomics Consortium

Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.

• DOI: 10.1038/s41380-021-01277-w
• 发表时间: 2021-12
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Halvorsen M;Szatkiewicz J;Mudgal P;Yu D;Psychiatric Genomics Consortium TS/OCD Working Group;Nordsletten AE;Mataix-Cols D;Mathews CA;Scharf JM;Mattheisen M;Robertson MM;McQuillin A;Crowley JJ
• 通讯作者: Crowley JJ