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.

Autor: Gorelik AJ; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Paul SE; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Karcher NR; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA., Johnson EC; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA., Nagella I; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Blaydon L; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Modi H; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Hansen IS; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA., Colbert SMC; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA., Baranger DAA; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Norton SA; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Spears I; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Gordon B; Department of Radiology, Washington University in Saint Louis, 660 South Euclid Ave, Box 8225, St. Louis, MO, 63110, USA.; Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University, St Louis, MO, USA., Zhang W; Department of Radiology, Washington University in Saint Louis, 660 South Euclid Ave, Box 8225, St. Louis, MO, 63110, USA., Hill PL; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Oltmanns TF; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Bijsterbosch JD; Department of Radiology, Washington University in Saint Louis, 660 South Euclid Ave, Box 8225, St. Louis, MO, 63110, USA., Agrawal A; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA., Hatoum AS; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA., Bogdan R; Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA. rbogdan@wustl.edu.
Jazyk: angličtina
Zdroj: Behavior genetics [Behav Genet] 2023 May; Vol. 53 (3), pp. 249-264. Date of Electronic Publication: 2023 Apr 18.
DOI: 10.1007/s10519-023-10140-3
Abstrakt: 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 Development SM 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 (AD PRS-APOE ), and an interaction between AD PRS-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 p fdr  > 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.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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