Mapping gene by early life stress interactions on child subcortical brain structures: A genome-wide prospective study (Record no. 485)
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042 ## - AUTHENTICATION CODE | |
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Authentication code | dc |
100 10 - MAIN ENTRY--PERSONAL NAME | |
Personal name | Bolhuis, Koen |
Relator term | author |
9 (RLIN) | 2940 |
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Title | Mapping gene by early life stress interactions on child subcortical brain structures: A genome-wide prospective study |
260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
Date of publication, distribution, etc. | 2022-11-16. |
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General note | /pmc/articles/PMC7614163/ |
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General note | /pubmed/36777645 |
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Summary, etc. | BACKGROUND: Although it is well-established that both genetics and the environment influence brain development, they are typically examined separately. Here, we aimed to prospectively investigate the interactive effects of genetic variants-from a genome-wide approach-and early life stress (ELS) on child subcortical brain structures, and their association with subsequent mental health problems. METHOD: Primary analyses were conducted using data from the Generation R Study (N = 2257), including genotype and cumulative prenatal and postnatal ELS scores (encompassing life events, contextual risk, parental risk, interpersonal risk, direct victimisation). Neuroimaging data were collected at age 10 years, including intracranial and subcortical brain volumes (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus). Genome-wide association and genome-wide-by-environment interaction analyses (GWEIS, run separately for prenatal/postnatal ELS) were conducted for eight brain outcomes (i.e., 24 genome-wide analyses) in the Generation R Study (discovery). Polygenic scores (PGS) using the resulting weights were calculated in an independent (target) cohort (adolescent brain cognitive development Study; N = 10,751), to validate associations with corresponding subcortical volumes and examine links to later mother-reported internalising and externalising problems. RESULTS: One GWEIS-prenatal stress locus was associated with caudate volume (rs139505895, mapping onto PRSS12 and NDST3) and two GWEIS-postnatal stress loci with the accumbens (rs2397823 and rs3130008, mapping onto CUTA, SYNGAP1, and TABP). Functional annotation revealed that these genes play a role in neuronal plasticity and synaptic function, and have been implicated in neuro-developmental phenotypes, for example, intellectual disability, autism, and schizophrenia. None of these associations survived a more stringent correction for multiple testing across all analysis sets. In the validation sample, all PGS(genotype) were associated with their respective brain volumes, but no PGS(GxE) associated with any subcortical volume. None of the PGS associated with internalising or externalising problems. CONCLUSIONS: This study lends novel suggestive insights into gene-environment interplay on the developing brain as well as pointing to promising candidate loci for future replication and mechanistic studies. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited https://creativecommons.org/licenses/by/4.0/. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | https://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license. |
546 ## - LANGUAGE NOTE | |
Language note | en |
690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
Topical term or geographic name as entry element | Article |
655 7# - INDEX TERM--GENRE/FORM | |
Genre/form data or focus term | Text |
Source of term | local |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Mulder, Rosa H. |
Relator term | author |
9 (RLIN) | 2941 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | de Mol, Casper Louk |
Relator term | author |
9 (RLIN) | 2942 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Defina, Serena |
Relator term | author |
9 (RLIN) | 2943 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Warrier, Varun |
Relator term | author |
9 (RLIN) | 2944 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | White, Tonya |
Relator term | author |
9 (RLIN) | 2945 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Tiemeier, Henning |
Relator term | author |
9 (RLIN) | 2946 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Muetzel, Ryan L. |
Relator term | author |
9 (RLIN) | 2947 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Cecil, Charlotte A. M. |
Relator term | author |
9 (RLIN) | 2948 |
786 0# - DATA SOURCE ENTRY | |
Note | JCPP Adv |
856 41 - ELECTRONIC LOCATION AND ACCESS | |
Uniform Resource Identifier | <a href="http://dx.doi.org/10.1002/jcv2.12113">http://dx.doi.org/10.1002/jcv2.12113</a> |
Public note | Connect to this object online. |
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