TY - JOUR
T1 - Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment
AU - Trampush, Joey W.
AU - Lencz, Todd
AU - Knowles, Emma
AU - Davies, Gail
AU - Guha, Saurav
AU - Pe'er, Itsik
AU - Liewald, David C.
AU - Starr, John M.
AU - Djurovic, Srdjan
AU - Melle, Ingrid
AU - Sundet, Kjetil
AU - Christoforou, Andrea
AU - Reinvang, Ivar
AU - Mukherjee, Semanti
AU - Derosse, Pamela
AU - Lundervold, Astri
AU - Steen, Vidar M.
AU - John, Majnu
AU - Espeseth, Thomas
AU - Räikkönen, Katri
AU - Widen, Elisabeth
AU - Palotie, Aarno
AU - Eriksson, Johan G.
AU - Giegling, Ina
AU - Konte, Bettina
AU - Ikeda, Masashi
AU - Roussos, Panos
AU - Giakoumaki, Stella
AU - Burdick, Katherine E.
AU - Payton, Antony
AU - Ollier, William
AU - Horan, Mike
AU - Scult, Matthew
AU - Dickinson, Dwight
AU - Straub, Richard E.
AU - Donohoe, Gary
AU - Morris, Derek
AU - Corvin, Aiden
AU - Gill, Michael
AU - Hariri, Ahmad
AU - Weinberger, Daniel R.
AU - Pendleton, Neil
AU - Iwata, Nakao
AU - Darvasi, Ariel
AU - Bitsios, Panos
AU - Rujescu, Dan
AU - Lahti, Jari
AU - Le Hellard, Stephanie
AU - Keller, Matthew C.
AU - Andreassen, Ole A.
AU - Deary, Ian J.
AU - Glahn, David C.
AU - Malhotra, Anil K.
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P=1.47×10-4) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P=4.94×10-7), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P=1.65×10-9). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.
AB - Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P=1.47×10-4) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P=4.94×10-7), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P=1.65×10-9). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.
KW - Educational attainment
KW - GWAS
KW - General cognitive ability
KW - Genetics
KW - Neurocognition
KW - Proxy phenotype
UR - http://www.scopus.com/inward/record.url?scp=84930930569&partnerID=8YFLogxK
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U2 - 10.1002/ajmg.b.32319
DO - 10.1002/ajmg.b.32319
M3 - Article
C2 - 25951819
AN - SCOPUS:84930930569
SN - 1552-4841
VL - 168
SP - 363
EP - 373
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 5
ER -