Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO, 63130, USA.
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Behav Genet. 2023 May;53(3):249-264. doi: 10.1007/s10519-023-10140-3. Epub 2023 Apr 18.
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 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), and an interaction between AD 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 > 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.
遗传风险因素与晚发性阿尔茨海默病（AD）相关，与健康的年轻成年人的认知能力较低和海马体体积较小有关。然而，在儿童时期是否存在这些和其他关联尚不清楚。利用正在进行的青少年大脑认知发展研究（ABCD 研究®）中 5556 名经基因组确认的欧洲血统年轻人的基线数据，我们进行了全表型关联研究，估计了四个晚发性 AD 遗传风险指标（即 AD 多基因风险评分（PRS）、APOE rs429358 基因型、去除 APOE 区域的 AD PRS（AD）和 AD 与 APOE 基因型之间的相互作用）与 1687 种社会心理、行为和神经表型之间的关联，在进行多次检验校正后，没有发现显著关联（所有 p 值均大于 0.0002；所有 p 值均大于 0.07）。这些数据表明，AD 遗传风险在儿童中期可能不会表型化出现，或者影响比本样本检测到的要小。
