Abstract
Genetic risk for Late Onset Alzheimer Disease (AD) has been associated with lower cognition and smaller hippocampal volume in healthy young adults. However, whether these and other associations are present during childhood remains unclear. Using data from 5556 genomically-confirmed European ancestry youth who completed the baseline session of the ongoing the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®), our phenome-wide association study estimating associations between four indices of genetic risk for late-onset AD (i.e., AD polygenic risk scores (PRS), APOE rs429358 genotype, AD PRS with the APOE region removed (ADPRS-APOE), and an interaction between ADPRS-APOE and APOE genotype) and 1687 psychosocial, behavioral, and neural phenotypes revealed no significant associations after correction for multiple testing (all ps > 0.0002; all pfdr > 0.07). These data suggest that AD genetic risk may not phenotypically manifest during middle-childhood or that effects are smaller than this sample is powered to detect.
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Data availability
All ABCD data used in this study are available through the National Institute of Mental Health Data Archive (NDA), which may be accessed here: https://nda.nih.gov/.
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References
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Acknowledgements
We are thankful to families who have participated in the ABCD Study as well as study staff and investigators. We thank Carlos Cruchaga for guidance on APOE genotype coding.
Funding
This study was funded by R01DA054750 (RB, AA). AJG was supported by NSF DGE-213989. SEP was supported by F31AA029934. NRK was supported by K23MH12179201. ECJ was supported by K01DA051759. ASH was supported by K01AA030083. Data for this study were provided by the Adolescent Brain Cognitive Development (ABCD) study, which was funded by the National Institutes of Health (grants U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147) and additional federal partners (https://abcdstudy.org/federal-partners.html).
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AJG, SEP, NRK, IN, LB, ISH cleaned the phenotypic data. AJG, SEP, ECJ, SC, ASH cleaned the genomic data and calculated/coded genetic risk (i.e., PRS, APOE4). AJG, SEP, ASH conducted analyses. AJG and RB conceptualized the study and AJG, RB, ASH, ECJ, NRK, and SEP drafted the initial manuscript. All coauthors provided input on study conceptualization and edited the manuscript with important intellectual content.
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Aaron J. Gorelik, Sarah E. Paul, Nicole R. Karcher, Emma C. Johnson, Isha Nagella, Lauren Blaydon, Hailey Modi, Isabella S. Hansen, Sarah M.C. Colbert, David A.A. Baranger, Sara A. Norton, Isaiah Spears, Brian Gordon, Wei Zhang, Patrick L. Hill, Thomas F. Oltmanns, Janine D. Bjisterbosch, Arpana Agrawal, Alexander S. Hatoum, and Ryan Bogdan declare that they have no conflict of interest.
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Working with ABCD NDA data was approved by the Washington University in St. Louis Institutional Review Board: IRB ID#201708123.
Human and Animal Rights and Informed consent
All data was obtained through the Adolescent Brain and Cognitive Development study. Informed consent was handled by each site. The ABCD data is publicly available (secondary data analysis). Informed consent was obtained from each site before data collection from the Childs parent or guardian. Data was deanonymized before download via the public NDA App. ABCD has extensive protocols for participant consent, safety, and anonymity, see https://doi.org/10.1016/j.dcn.2017.06.005.
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Gorelik, A.J., Paul, S.E., Karcher, N.R. et al. A Phenome-Wide Association Study (PheWAS) of Late Onset Alzheimer Disease Genetic Risk in Children of European Ancestry at Middle Childhood: Results from the ABCD Study. Behav Genet 53, 249–264 (2023). https://doi.org/10.1007/s10519-023-10140-3
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DOI: https://doi.org/10.1007/s10519-023-10140-3