Genome-wide association analysis identifies common variants influencing infant brain volumes
Open accessAbstract
Genome-wide association studies (GWAS) of adolescents and adults are transforming our understanding of how genetic variants impact brain structure and psychiatric risk, but cannot address the reality that psychiatric disorders are unfolding developmental processes with origins in fetal life. To investigate how genetic variation impacts prenatal brain development, we conducted a GWAS of global brain tissue volumes in 561 infants. An intronic single-nucleotide polymorphism (SNP) in IGFBP7 (rs114518130) achieved genome-wide significance for gray matter volume ( P =4.15 × 10 −10 ). An intronic SNP in WWOX (rs10514437) neared genome-wide significance for white matter volume ( P =1.56 × 10 −8 ). Additional loci with small P -values included psychiatric GWAS associations and transcription factors expressed in developing brain. Genetic predisposition scores for schizophrenia and ASD, and the number of genes impacted by rare copy number variants (CNV burden) did not predict global brain tissue volumes. Integration of these results with large-scale neuroimaging GWAS in adolescents (PNC) and adults (ENIGMA2) suggests minimal overlap between common variants impacting brain volumes at different ages. Ultimately, by identifying genes contributing to adverse developmental phenotypes, it may be possible to adjust adverse trajectories, preventing or ameliorating psychiatric and developmental disorders.
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An intronic SNP in IGFBP7 (rs114518130) is significantly associated with grey-matter volume, with volume increasing with increasing dose of the G allele.
“an intronic single-nucleotide polymorphism (SNP) in IGFBP7 (rs114518130) was found to be significantly associated with grey-matter volume (volume increases with increasing dose of the G allele).”
From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [162]
The first GWAS of neonatal brain structure requires independent replication, particularly for the imputed low-frequency IGFBP7 SNP absent from the largest racial/ethnic group.
“This is the first study of its kind162 and independent replication is crucial, especially for the IGFBP7 intronic SNP, which was imputed, has a low minor allele frequency, and was not present in the largest racial/ethnic group in the study.”
From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [162]
An intronic SNP in WWOX (rs10514437) fell just short of genome-wide significance for white matter.
“An intronic SNP in WWOX (rs10514437) fell just short of genome-wide significance for white matter.”
From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [162]
Common variants associated with neonatal brain structure have been identified using a genome-wide association study.
“common variants associated with neonatal brain structure have been identified using a genome-wide association study (GWAS) approach162.”
From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [162]
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SNORD116 and growth hormone therapy impact IGFBP7 in Prader–Willi syndrome
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- Authors
- Xia, K., Zhang, J., Ahn, M., Jha, S., Crowley, J. J., Szatkiewicz, J., Li, T., Zou, F., Zhu, H., Hibar, D., Thompson, P., ENIGMA Consortium, Sullivan, P. F., Styner, M., Gilmore, J. H., & Knickmeyer, R. C.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Southern California (US)
- Corresponding author
- Knickmeyer, R C
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2017-08-01
- Volume
- 7
- Issue
- 8
- Pages
- e1188-e1188
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC5611727
- OpenAlex
- W2740817192
- Cited by
- 30
- References
- 66
- Citations by year
- 2025: 3 · 2023: 4 · 2022: 2 · 2021: 7 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 1
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Alliance for Research on Schizophrenia and Depression (HD053000, MH070890)
- Wellcome Trust (U54 EB020403)
- John and Polly Sparks Foundation
- National Institutes of Health (DMS-1407655, SES-1357666, HD-003110, MH070890, EB005149, EB005149-01, MH064065, RR025747, EB020403)
- National Institute of Mental Health (RC2MH089983, U01MH070890, P50MH064065, RC2MH089924, R01MH092335, R01MH106611, R21MH099370, R01MH086633, R01MH070890, K01MH083045)
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke (T32NS007431)
- National Institute of Biomedical Imaging and Bioengineering (U54EB005149, U54EB020403, P41EB015922)
- National Center for Research Resources (UL1RR025747)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD053000, P30HD003110)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- gray matter volume, white matter volume, fetal brain development, IGFBP7, WWOX, single nucleotide polymorphisms, schizophrenia, autism spectrum disorder, copy number variation, neuroimaging genetics
- MeSH terms
- Brain, Female, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Male, Organ Size, Insulin-Like Growth Factor Binding Proteins, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Neuroimaging
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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