Περίληψη:
The complex nature of human cognition has resulted in cognitive genomics
lagging behind many other fields in terms of gene discovery using
genome-wide association study (GWAS) methods. In an attempt to overcome
these barriers, the current study utilized GWAS meta-analysis to examine
the association of common genetic variation (similar to 8M
single-nucleotide polymorphisms (SNP) with minor allele frequency >=
1%) to general cognitive function in a sample of 35 298 healthy
individuals of European ancestry across 24 cohorts in the Cognitive
Genomics Consortium (COGENT). In addition, we utilized individual SNP
lookups and polygenic score analyses to identify genetic overlap with
other relevant neurobehavioral phenotypes. Our primary GWAS
meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the
CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome
1) associated with cognitive performance at the genome-wide significance
level (P<5x10(-8)). Gene-based analysis identified an additional three
Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1
and 1p13.3. Altogether, common variation across the genome resulted in a
conservatively estimated SNP heritability of 21.5% (s.e. = 0.01%) for
general cognitive function. Integration with prior GWAS of cognitive
performance and educational attainment yielded several additional
significant loci. Finally, we found robust polygenic correlations
between cognitive performance and educational attainment, several
psychiatric disorders, birth length/weight and smoking behavior, as well
as a novel genetic association to the personality trait of openness.
These data provide new insight into the genetics of neurocognitive
function with relevance to understanding the pathophysiology of
neuropsychiatric illness.
Συγγραφείς:
Trampush, J. W.
Yang, M. L. Z.
Yu, J.
Knowles, E. and
Davies, G.
Liewald, D. C.
Starr, J. M.
Djurovic, S. and
Melle, I.
Sundet, K.
Christoforou, A.
Reinvang, I. and
DeRosse, P.
Lundervold, A. J.
Steen, V. M.
Espeseth, T. and
Raikkonen, K.
Widen, E.
Palotie, A.
Eriksson, J. G. and
Giegling, I.
Konte, B.
Roussos, P.
Giakoumaki, S. and
Burdick, K. E.
Payton, A.
Ollier, W.
Horan, M. and
Chiba-Falek, O.
Attix, D. K.
Need, A. C.
Cirulli, E. T. and
Voineskos, A. N.
Stefanis, N. C.
Avramopoulos, D. and
Hatzimanolis, A.
Arking, D. E.
Smyrnis, N.
Bilder, R. M. and
Freimer, N. A.
Cannon, T. D.
London, E.
Poldrack, R. A. and
Sabb, F. W.
Congdon, E.
Conley, E. D.
Scult, M. A. and
Dickinson, D.
Straub, R. E.
Donohoe, G.
Morris, D. and
Corvin, A.
Gill, M.
Hariri, A. R.
Weinberger, D. R. and
Pendleton, N.
Bitsios, P.
Rujescu, D.
Lahti, J.
Le
Hellard, S.
Keller, M. C.
Andreassen, O. A.
Deary, I. J. and
Glahn, D. C.
Malhotra, A. K.
Lencz, T.
