TY - JOUR
T1 - Meta-analysis of epigenome-wide association studies of cognitive abilities
AU - Marioni, Riccardo E.
AU - McRae, Allan F.
AU - Bressler, Jan
AU - Colicino, Elena
AU - Hannon, Eilis
AU - Li, Shuo
AU - Prada, Diddier
AU - Smith, Jennifer A.
AU - Trevisi, Letizia
AU - Tsai, Pei Chien
AU - Vojinovic, Dina
AU - Simino, Jeannette
AU - Levy, Daniel
AU - Liu, Chunyu
AU - Mendelson, Michael
AU - Satizabal, Claudia L.
AU - Yang, Qiong
AU - Jhun, Min A.
AU - Kardia, Sharon L.R.
AU - Zhao, Wei
AU - Bandinelli, Stefania
AU - Ferrucci, Luigi
AU - Hernandez, Dena G.
AU - Singleton, Andrew B.
AU - Harris, Sarah E.
AU - Starr, John M.
AU - Kiel, Douglas P.
AU - McLean, Robert R.
AU - Just, Allan C.
AU - Schwartz, Joel
AU - Spiro, Avron
AU - Vokonas, Pantel
AU - Amin, Najaf
AU - Ikram, M. Arfan
AU - Uitterlinden, Andre G.
AU - van Meurs, Joyce B.J.
AU - Spector, Tim D.
AU - Steves, Claire
AU - Baccarelli, Andrea A.
AU - Bell, Jordana T.
AU - van Duijn, Cornelia M.
AU - Fornage, Myriam
AU - Hsu, Yi Hsiang
AU - Mill, Jonathan
AU - Mosley, Thomas H.
AU - Seshadri, Sudha
AU - Deary, Ian J.
N1 - Publisher Copyright:
© 2017, The Author(s).
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood-based DNA methylation levels at ~420,000 CpG sites were performed for seven measures of cognitive functioning using data from 11 cohorts. CpGs that passed a Bonferroni correction, adjusting for the number of CpGs and cognitive tests, were assessed for: longitudinal change; being under genetic control (methylation QTLs); and associations with brain health (structural MRI), brain methylation and Alzheimer's disease pathology. Across the seven measures of cognitive functioning (meta-analysis n range: 2557–6809), there were epigenome-wide significant (P < 1.7 × 10-8) associations for global cognitive function (cg21450381, P = 1.6 × 10-8), and phonemic verbal fluency (cg12507869, P = 2.5 × 10-9). The CpGs are located in an intergenic region on chromosome 12 and the INPP5A gene on chromosome 10, respectively. Both probes have moderate correlations (~0.4) with brain methylation in Brodmann area 20 (ventral temporal cortex). Neither probe showed evidence of longitudinal change in late-life or associations with white matter brain MRI measures in one cohort with these data. A methylation QTL analysis suggested that rs113565688 was a cis methylation QTL for cg12507869 (P = 5 × 10-5 and 4 × 10-13 in two lookup cohorts). We demonstrate a link between blood-based DNA methylation and measures of phonemic verbal fluency and global cognitive ability. Further research is warranted to understand the mechanisms linking genomic regulatory changes with cognitive function to health and disease.
AB - Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood-based DNA methylation levels at ~420,000 CpG sites were performed for seven measures of cognitive functioning using data from 11 cohorts. CpGs that passed a Bonferroni correction, adjusting for the number of CpGs and cognitive tests, were assessed for: longitudinal change; being under genetic control (methylation QTLs); and associations with brain health (structural MRI), brain methylation and Alzheimer's disease pathology. Across the seven measures of cognitive functioning (meta-analysis n range: 2557–6809), there were epigenome-wide significant (P < 1.7 × 10-8) associations for global cognitive function (cg21450381, P = 1.6 × 10-8), and phonemic verbal fluency (cg12507869, P = 2.5 × 10-9). The CpGs are located in an intergenic region on chromosome 12 and the INPP5A gene on chromosome 10, respectively. Both probes have moderate correlations (~0.4) with brain methylation in Brodmann area 20 (ventral temporal cortex). Neither probe showed evidence of longitudinal change in late-life or associations with white matter brain MRI measures in one cohort with these data. A methylation QTL analysis suggested that rs113565688 was a cis methylation QTL for cg12507869 (P = 5 × 10-5 and 4 × 10-13 in two lookup cohorts). We demonstrate a link between blood-based DNA methylation and measures of phonemic verbal fluency and global cognitive ability. Further research is warranted to understand the mechanisms linking genomic regulatory changes with cognitive function to health and disease.
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U2 - 10.1038/s41380-017-0008-y
DO - 10.1038/s41380-017-0008-y
M3 - Article
C2 - 29311653
AN - SCOPUS:85053054360
SN - 1359-4184
VL - 23
SP - 2133
EP - 2144
JO - Molecular psychiatry
JF - Molecular psychiatry
IS - 11
ER -