A Genome-wide Association Meta-analysis of Preschool Internalizing Problems

被引：42

作者：

Benke, Kelly S. ^{[1
,2
]}

Nivard, Michel G. ^{[3
,4
]}

Velders, Fleur P. ^{[5
,6
]}

Walters, Raymond K. ^{[7
]}

Pappa, Irene ^{[8
,9
]}

Scheet, Paul A. ^{[10
]}

Xiao, Xiangjun ^{[10
]}

Ehli, Erik A. ^{[11
]}

Palmer, Lyle J. ^{[12
,13
]}

Whitehouse, Andrew J. O. ^{[14
,15
,16
]}

Verhulst, Frank C. ^{[5
]}

Jaddoe, Vincent W. ^{[5
,17
]}

Rivadeneira, Fernando ^{[5
]}

Groen-Blokhuis, Maria M. ^{[3
,18
]}

van Beijsterveldt, Catharina E. M. ^{[3
]}

Davies, Gareth E. ^{[11
]}

Hudziak, James J. ^{[19
,20
]}

Lubke, Gitta H. ^{[3
,7
]}

Boomsma, Dorret I. ^{[18
,21
]}

Pennell, Craig E. ^{[22
]}

Tiemeier, Henning ^{[5
]}

Middeldorp, Christel M. ^{[21
,23
]}

机构：

[1] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA

[2] Univ Toronto, Samuel Lunenfeld Res Inst, Toronto, ON, Canada

[3] Vrije Univ Amsterdam, Amsterdam, Netherlands

[4] Vrije Univ Amsterdam, Neurosci Campus Amsterdam, Amsterdam, Netherlands

[5] Erasmus MC, Rotterdam, Netherlands

[6] Erasmus MC, Generat Study Grp R, Rotterdam, Netherlands

[7] Univ Notre Dame, Notre Dame, IN 46556 USA

[8] Erasmus Univ, Generat Study Grp R, Sch Pedag & Educ Sci, Rotterdam, Netherlands

[9] Erasmus Univ, Med Ctr, Sophia Childrens Hosp, NL-3000 DR Rotterdam, Netherlands

[10] Univ Texas MD Anderson Canc Ctr, Houston, TX USA

[11] Avera Inst Human Genet, Sioux Falls, SD USA

[12] Univ Toronto, Samuel Lunenfeld Res Inst, Toronto, ON, Canada

[13] Ontario Inst Canc Res, Toronto, ON, Canada

[14] Telethon Inst Child Hlth Res, Subiaco, WA, Australia

[15] Univ Western Australia, Ctr Child Hlth Res, Perth, WA 6009, Australia

[16] Univ Western Australia, Sch Psychol, Crawley, WA, Australia

[17] Generat R Study Grp, Rotterdam, Netherlands

[18] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands

[19] Vermont Ctr Children Youth & Families, Burlington, VT USA

[20] Univ Vermont, Coll Med, Burlington, VT 05405 USA

[21] Vrije Univ Amsterdam, Neurosci Campus Amsterdam, Amsterdam, Netherlands

[22] Univ Western Australia, Sch Womens & Infants Hlth, Nedlands, WA 6009, Australia

[23] Vrije Univ Amsterdam, Med Ctr, GGZinGeest, Amsterdam, Netherlands

来源：

JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY | 2014年 / 53卷 / 06期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 欧洲研究理事会; 美国国家科学基金会;

关键词：

GWA study; internalizing problems; pcsk2; variance explained; GCTA; NETHERLANDS TWIN REGISTER; MAJOR DEPRESSIVE DISORDER; PSYCHIATRIC-DISORDERS; GENETIC EPIDEMIOLOGY; EARLY-CHILDHOOD; GENERATION-R; PCSK2; GENE; HERITABILITY; ANXIETY; COHORT;

D O I：

10.1016/j.jaac.2013.12.028

中图分类号：

B844 [发展心理学（人类心理学）];

学科分类号：

040202 ;

摘要：

Objective: Preschool internalizing problems (ENT) are highly heritable and moderately genetically stable from childhood into adulthood. Gene-finding studies are scarce. In this study, the influence of genome-wide measured single nucleotide polymorphisms (SNPs) was investigated in 3 cohorts (total N = 4,596 children) in which TNT was assessed with the same instrument, the Child Behavior Checklist (CBCL). Method: First, genome-wide association (GWA) results were used for density estimation and genome-wide complex trait analysis (GCTA) to calculate the variance explained by all SNPs. Next, a fixed-effect inverse variance meta-analysis of the 3 GWA analyses was carried out. Finally, the overlap in results with prior GWA studies of childhood and adulthood psychiatric disorders and treatment responses was tested by examining whether SNPs associated with these traits jointly showed a significant signal for INT. Results: Genome-wide SNPs explained 13% to 43% of the total variance. This indicates that the genetic architecture of INT mirrors the polygenic model underlying adult psychiatric traits. The meta-analysis did not yield a genome-wide significant signal but was suggestive for the PCSK2 gene located on chromosome 20p12.1. SNPs associated with other psychiatric disorders appeared to be enriched for signals with TNT = (lambda = 1.26, p < .03). Conclusion: Our study provides evidence that INT is influenced by many common genetic variants, each with a very small effect, and that, even as early as age 3, genetic variants influencing INT overlap with variants that play a role in childhood and adulthood psychiatric disorders.

引用

页码：667 / 676

页数：10

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