Copy Number Variant Risk Scores Associated With Cognition, Psychopathology, and Brain Structure in Youths in the Philadelphia Neurodevelopmental Cohort

神经认知 精神病理学 拷贝数变化 队列 心理学 精神科 认知 医学 临床心理学 遗传学 内科学 基因组 生物 基因
作者
Aaron Alexander‐Bloch,Guillaume Huguet,Laura M. Schultz,Nicholas Huffnagle,Sébastien Jacquemont,Jakob Seidlitz,Zohra Saci,Tyler M. Moore,Richard A.I. Bethlehem,Josephine Mollon,Emma Knowles,Armin Raznahan,Alison Merikangas,Barbara H. Chaiyachati,Harshini Raman,J. Eric Schmitt,Ran Barzilay,Monica E. Calkins,Russel T. Shinohara,Theodore D. Satterthwaite,Ruben C. Gur,David C. Glahn,Laura Almasy,Raquel E. Gur,Håkon Håkonarson,Joseph Glessner
出处
期刊:JAMA Psychiatry [American Medical Association]
卷期号:79 (7): 699-699 被引量:21
标识
DOI:10.1001/jamapsychiatry.2022.1017
摘要

Psychiatric and cognitive phenotypes have been associated with a range of specific, rare copy number variants (CNVs). Moreover, IQ is strongly associated with CNV risk scores that model the predicted risk of CNVs across the genome. But the utility of CNV risk scores for psychiatric phenotypes has been sparsely examined.To determine how CNV risk scores, common genetic variation indexed by polygenic scores (PGSs), and environmental factors combine to associate with cognition and psychopathology in a community sample.The Philadelphia Neurodevelopmental Cohort is a community-based study examining genetics, psychopathology, neurocognition, and neuroimaging. Participants were recruited through the Children's Hospital of Philadelphia pediatric network. Participants with stable health and fluency in English underwent genotypic and phenotypic characterization from November 5, 2009, through December 30, 2011. Data were analyzed from January 1 through July 30, 2021.The study examined (1) CNV risk scores derived from models of burden, predicted intolerance, and gene dosage sensitivity; (2) PGSs from genomewide association studies related to developmental outcomes; and (3) environmental factors, including trauma exposure and neighborhood socioeconomic status.The study examined (1) neurocognition, with the Penn Computerized Neurocognitive Battery; (2) psychopathology, with structured interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children; and (3) brain volume, with magnetic resonance imaging.Participants included 9498 youths aged 8 to 21 years; 4906 (51.7%) were female, and the mean (SD) age was 14.2 (3.7) years. After quality control, 18 185 total CNVs greater than 50 kilobases (10 517 deletions and 7668 duplications) were identified in 7101 unrelated participants genotyped on Illumina arrays. In these participants, elevated CNV risk scores were associated with lower overall accuracy on cognitive tests (standardized β = 0.12; 95% CI, 0.10-0.14; P = 7.41 × 10-26); lower accuracy across a range of cognitive subdomains; increased overall psychopathology; increased psychosis-spectrum symptoms; and higher deviation from a normative developmental model of brain volume. Statistical models of developmental outcomes were significantly improved when CNV risk scores were combined with PGSs and environmental factors.In this study, elevated CNV risk scores were associated with lower cognitive ability, higher psychopathology including psychosis-spectrum symptoms, and greater deviations from normative magnetic resonance imaging models of brain development. Together, these results represent a step toward synthesizing rare genetic, common genetic, and environmental factors to understand clinically relevant outcomes in youth.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
liyi发布了新的文献求助10
1秒前
1秒前
2秒前
Owen应助兰禅子采纳,获得10
2秒前
感谢董璐转发科研通微信,获得积分50
2秒前
Akim应助谷氨酸采纳,获得30
3秒前
4秒前
Sk发布了新的文献求助10
4秒前
李李完成签到 ,获得积分10
4秒前
BCyu完成签到 ,获得积分10
5秒前
5秒前
7秒前
pjs完成签到,获得积分10
7秒前
7秒前
UUSee完成签到,获得积分10
7秒前
7秒前
7秒前
在水一方应助小林采纳,获得10
7秒前
钱财实景发布了新的文献求助50
7秒前
8秒前
czj完成签到 ,获得积分10
8秒前
可可西里发布了新的文献求助10
8秒前
顺利涵菡发布了新的文献求助10
9秒前
yuaner发布了新的文献求助10
10秒前
感谢shenxiaohui转发科研通微信,获得积分50
10秒前
10秒前
欧啦啦发布了新的文献求助10
11秒前
香蕉觅云应助abne采纳,获得10
11秒前
dachengzi发布了新的文献求助10
12秒前
12秒前
12秒前
慕青应助Bonnie采纳,获得10
13秒前
14秒前
14秒前
桥下完成签到,获得积分10
14秒前
14秒前
感谢jsyfanature转发科研通微信,获得积分50
15秒前
杨杨发布了新的文献求助10
15秒前
15秒前
16秒前
高分求助中
Sustainability in Tides Chemistry 2800
Kinetics of the Esterification Between 2-[(4-hydroxybutoxy)carbonyl] Benzoic Acid with 1,4-Butanediol: Tetrabutyl Orthotitanate as Catalyst 1000
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Handbook of Qualitative Cross-Cultural Research Methods 600
Very-high-order BVD Schemes Using β-variable THINC Method 568
Chen Hansheng: China’s Last Romantic Revolutionary 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3138933
求助须知:如何正确求助?哪些是违规求助? 2789871
关于积分的说明 7793019
捐赠科研通 2446289
什么是DOI,文献DOI怎么找? 1301004
科研通“疑难数据库(出版商)”最低求助积分说明 626087
版权声明 601096