期刊
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
卷 53, 期 6, 页码 667-676出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jaac.2013.12.028
关键词
GWA study; internalizing problems; pcsk2; variance explained; GCTA
资金
- American Recovery and Reinvestment Act (ARRA) project [RC2 2MH08995]
- Netherlands Organisation for Scientific Research Spinozapremie prize [NWO/SPI 56-464-14192]
- NWO Center for Medical Systems Biology (CMSB)
- Twin-family database for behavior genetics and genomics studies [NWO 480-04-004]
- Genetic and Family Influences on Adolescent Psychopathology and Wellness [NWO 463-06-001]
- Netherlands Bioinformatics Centre (NBIC) Bioassist [NWO-NBIC/BioAssist/RK/2008.024]
- Biobanking and Biomolecular Resources Research Infrastructure [NWO 184.021.007]
- Genetic influences on stability and change in psychopathology from childhood to your adulthood [ZonMW 91210020]
- Genetics of Mental Illness (European Research Council) [ERC-230374]
- National Health and Medical Research Council (NHMRC)
- University of Western Australia (UWA)
- Curlin University
- UWA Faculty of Medicine, Dentistry and Health Sciences
- Raine Medical Research Foundation
- Telethon Institute for Child Health Research
- Women's and Infants Research Foundation
- NHMRC [572613, 1004065]
- Erasmus Medical Center Rotterdam
- Erasmus University Rotterdam
- Netherlands Organization for Health Research and Development [ZonMw 10.000.1003]
- Netherlands Organisation for Scientific Research
- Ministry of Health, Welfare, and Sport
- Ministry of Youth and Families
- Sophia Foundation for Scientific Research (SKZ Foundation) [491]
- NWO ZonMW VIDI grant [017.106.370]
- Direct For Social, Behav & Economic Scie
- Division Of Behavioral and Cognitive Sci [1229450] Funding Source: National Science Foundation
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.
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