TY - JOUR
T1 - Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging
AU - Knol, Maria J.
AU - Heshmatollah, Alis
AU - Cremers, Lotte G.M.
AU - Ikram, M. Kamran
AU - Uitterlinden, André G.
AU - van Duijn, Cornelia M.
AU - Niessen, Wiro J.
AU - Vernooij, Meike W.
AU - Arfan Ikram, M.
AU - Adams, Hieab H.H.
N1 - Publisher Copyright:
© Knol et al.
PY - 2019/3/15
Y1 - 2019/3/15
N2 - Cognition in adults shows variation due to developmental and degenerative components. A recent genomewide association study identified genetic variants for general cognitive function in 148 independent loci. Here, we aimed to elucidate possible developmental and neurodegenerative pathways underlying these genetic variants by relating them to functional, clinical and neuroimaging outcomes. This study was conducted within the population-based Rotterdam Study (N=11,496, mean age 65.3±9.9 years, 58.0% female). We used lead variants for general cognitive function to construct a polygenic score (PGS), and additionally excluded developmental variants at multiple significance thresholds. A higher PGS was related to more years of education (β=0.29, p=4.3×10 -7 ) and a larger intracranial volume (β=0.05, p=7.5×10 -4 ). To a smaller extent, the PGS was associated with less cognitive decline (βΔG-factor=0.03, p=1.3×10 -3 ), which became non-significant after adjusting for education (p=1.6×10 -2 ). No associations were found with daily functioning, dementia, parkinsonism, stroke or microstructural white matter integrity. Excluding developmental variants attenuated nearly all associations. In conclusion, this study suggests that the genetic variants identified for general cognitive function are acting mainly through the developmental pathway of cognition. Therefore, cognition, assessed cross-sectionally, seems to have limited value as a biomarker for neurodegeneration.
AB - Cognition in adults shows variation due to developmental and degenerative components. A recent genomewide association study identified genetic variants for general cognitive function in 148 independent loci. Here, we aimed to elucidate possible developmental and neurodegenerative pathways underlying these genetic variants by relating them to functional, clinical and neuroimaging outcomes. This study was conducted within the population-based Rotterdam Study (N=11,496, mean age 65.3±9.9 years, 58.0% female). We used lead variants for general cognitive function to construct a polygenic score (PGS), and additionally excluded developmental variants at multiple significance thresholds. A higher PGS was related to more years of education (β=0.29, p=4.3×10 -7 ) and a larger intracranial volume (β=0.05, p=7.5×10 -4 ). To a smaller extent, the PGS was associated with less cognitive decline (βΔG-factor=0.03, p=1.3×10 -3 ), which became non-significant after adjusting for education (p=1.6×10 -2 ). No associations were found with daily functioning, dementia, parkinsonism, stroke or microstructural white matter integrity. Excluding developmental variants attenuated nearly all associations. In conclusion, this study suggests that the genetic variants identified for general cognitive function are acting mainly through the developmental pathway of cognition. Therefore, cognition, assessed cross-sectionally, seems to have limited value as a biomarker for neurodegeneration.
KW - Cognition
KW - Cognitive reserve
KW - Genetics
KW - Neuroimaging
KW - Neurological disorders
UR - http://www.scopus.com/inward/record.url?scp=85062986905&partnerID=8YFLogxK
U2 - 10.18632/aging.101844
DO - 10.18632/aging.101844
M3 - Article
C2 - 30830859
AN - SCOPUS:85062986905
SN - 1945-4589
VL - 11
SP - 1440
EP - 1456
JO - Aging
JF - Aging
IS - 5
ER -