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

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. Bijsterbosch; Arpana Agrawal; Alexander S. Hatoum; Ryan Bogdan

doi:10.1007/s10519-023-10140-3

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

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. Bijsterbosch, Arpana Agrawal, Alexander S. Hatoum, Ryan Bogdan

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1 Scopus citations

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 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.

Original language	English
Pages (from-to)	249-264
Number of pages	16
Journal	Behavior genetics
Volume	53
Issue number	3
DOIs	https://doi.org/10.1007/s10519-023-10140-3
State	Published - May 2023

Keywords

APOE
Alzheimer disease
Imaging
Middle childhood
Phenome-wide association study
Polygenic risk scores

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10.1007/s10519-023-10140-3

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Gorelik, A. J., Paul, S. E., Karcher, N. R., Johnson, E. C., Nagella, I., Blaydon, L., Modi, H., Hansen, I. S., Colbert, S. M. C., Baranger, D. A. A., Norton, S. A., Spears, I., Gordon, B., Zhang, W., Hill, P. L., Oltmanns, T. F., Bijsterbosch, J. D., Agrawal, A., Hatoum, A. S., & Bogdan, R. (2023). 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. Behavior genetics, 53(3), 249-264. https://doi.org/10.1007/s10519-023-10140-3

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title = "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",

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{\textregistered}), 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.",

keywords = "APOE, Alzheimer disease, Imaging, Middle childhood, Phenome-wide association study, Polygenic risk scores",

author = "Gorelik, {Aaron J.} and Paul, {Sarah E.} and Karcher, {Nicole R.} and Johnson, {Emma C.} and Isha Nagella and Lauren Blaydon and Hailey Modi and Hansen, {Isabella S.} and Colbert, {Sarah M.C.} and Baranger, {David A.A.} and Norton, {Sara A.} and Isaiah Spears and Brian Gordon and Wei Zhang and Hill, {Patrick L.} and Oltmanns, {Thomas F.} and Bijsterbosch, {Janine D.} and Arpana Agrawal and Hatoum, {Alexander S.} and Ryan Bogdan",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2023",

month = may,

doi = "10.1007/s10519-023-10140-3",

language = "English",

volume = "53",

pages = "249--264",

journal = "Behavior genetics",

issn = "0001-8244",

number = "3",

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Gorelik, AJ, Paul, SE, Karcher, NR , Johnson, EC, Nagella, I, Blaydon, L, Modi, H, Hansen, IS, Colbert, SMC, Baranger, DAA, Norton, SA, Spears, I, Gordon, B, Zhang, W, Hill, PL, Oltmanns, TF, Bijsterbosch, JD , Agrawal, A , Hatoum, AS & Bogdan, R 2023, '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', Behavior genetics, vol. 53, no. 3, pp. 249-264. https://doi.org/10.1007/s10519-023-10140-3

TY - JOUR

T1 - A Phenome-Wide Association Study (PheWAS) of Late Onset Alzheimer Disease Genetic Risk in Children of European Ancestry at Middle Childhood

T2 - Results from the ABCD Study

AU - Gorelik, Aaron J.

AU - Paul, Sarah E.

AU - Karcher, Nicole R.

AU - Johnson, Emma C.

AU - Nagella, Isha

AU - Blaydon, Lauren

AU - Modi, Hailey

AU - Hansen, Isabella S.

AU - Colbert, Sarah M.C.

AU - Baranger, David A.A.

AU - Norton, Sara A.

AU - Spears, Isaiah

AU - Gordon, Brian

AU - Zhang, Wei

AU - Hill, Patrick L.

AU - Oltmanns, Thomas F.

AU - Bijsterbosch, Janine D.

AU - Agrawal, Arpana

AU - Hatoum, Alexander S.

AU - Bogdan, Ryan

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

KW - APOE

KW - Alzheimer disease

KW - Imaging

KW - Middle childhood

KW - Phenome-wide association study

KW - Polygenic risk scores

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U2 - 10.1007/s10519-023-10140-3

DO - 10.1007/s10519-023-10140-3

M3 - Article

C2 - 37071275

AN - SCOPUS:85153037626

SN - 0001-8244

VL - 53

SP - 249

EP - 264

JO - Behavior genetics

JF - Behavior genetics

IS - 3

ER -

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

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Keywords

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