Title | Implication of the APP Gene in Intellectual Abilities. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Myrum, C, Nikolaienko, ii, O, Bramham, CR, Haavik, J, Zayats, T |
Journal | J Alzheimers Dis |
Volume | 59 |
Issue | 2 |
Pagination | 723-735 |
Date Published | 2017 |
ISSN | 1875-8908 |
Abstract | BACKGROUND: Cognitive functions are highly heritable and polygenic, though the source of this genetic influence is unclear. On the neurobiological level, these functions rely on effective neuroplasticity, in which the activity-regulated cytoskeleton associated protein (ARC) plays an essential role. OBJECTIVES: To examine whether the ARC gene complex may contribute to the genetic components of intellectual function given the crucial role of ARC in brain plasticity and memory formation. METHODS: The ARC complex was tested for association with intelligence (IQ) in children from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5,165). As Alzheimer's disease (AD) shares genetics with cognitive functioning, the association was followed up in an AD sample (17,008 cases, 37,154 controls). RESULTS: The ARC complex revealed association with verbal and total IQ (empirical p = 0.027 and 0.041, respectively) in the ALSPAC. The strongest single variant signal (rs2830077; empirical p = 0.018), within the APP gene, was confirmed in the AD sample (p = 2.76E-03). Functional analyses of this variant showed its preferential binding to the transcription factor CP2. DISCUSSION: This study implicates APP in childhood IQ. While follow-up studies are needed, this observation could help elucidate the etiology of disorders associated with cognitive dysfunction, such as AD. |
DOI | 10.3233/JAD-170049 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 28671113 |
PubMed Central ID | PMC5523840 |
Grant List | U24 AG021886 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States MC_PC_15018 / / Medical Research Council / United Kingdom R01 AG033193 / AG / NIA NIH HHS / United States / / Wellcome Trust / United Kingdom |