Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment

Joey W. Trampush, Todd Lencz, Emma Knowles, Gail Davies, Saurav Guha, Itsik Pe'er, David C. Liewald, John M. Starr, Srdjan Djurovic, Ingrid Melle, Kjetil Sundet, Andrea Christoforou, Ivar Reinvang, Semanti Mukherjee, Pamela Derosse, Astri Lundervold, Vidar M. Steen, Majnu John, Thomas Espeseth, Katri RäikkönenElisabeth Widen, Aarno Palotie, Johan G. Eriksson, Ina Giegling, Bettina Konte, Masashi Ikeda, Panos Roussos, Stella Giakoumaki, Katherine E. Burdick, Antony Payton, William Ollier, Mike Horan, Matthew Scult, Dwight Dickinson, Richard E. Straub, Gary Donohoe, Derek Morris, Aiden Corvin, Michael Gill, Ahmad Hariri, Daniel R. Weinberger, Neil Pendleton, Nakao Iwata, Ariel Darvasi, Panos Bitsios, Dan Rujescu, Jari Lahti, Stephanie Le Hellard, Matthew C. Keller, Ole A. Andreassen, Ian J. Deary, David C. Glahn, Anil K. Malhotra

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)363-373
Number of pages11
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume168
Issue number5
DOIs
Publication statusPublished - 01-07-2015

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Aptitude
Genetic Loci
Genome-Wide Association Study
Psychiatry
Cognition
Multifactorial Inheritance
Education
Educational Status
Genomics
Sample Size
Single Nucleotide Polymorphism
Meta-Analysis
Chromosomes
Genome

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Trampush, Joey W. ; Lencz, Todd ; Knowles, Emma ; Davies, Gail ; Guha, Saurav ; Pe'er, Itsik ; Liewald, David C. ; Starr, John M. ; Djurovic, Srdjan ; Melle, Ingrid ; Sundet, Kjetil ; Christoforou, Andrea ; Reinvang, Ivar ; Mukherjee, Semanti ; Derosse, Pamela ; Lundervold, Astri ; Steen, Vidar M. ; John, Majnu ; Espeseth, Thomas ; Räikkönen, Katri ; Widen, Elisabeth ; Palotie, Aarno ; Eriksson, Johan G. ; Giegling, Ina ; Konte, Bettina ; Ikeda, Masashi ; Roussos, Panos ; Giakoumaki, Stella ; Burdick, Katherine E. ; Payton, Antony ; Ollier, William ; Horan, Mike ; Scult, Matthew ; Dickinson, Dwight ; Straub, Richard E. ; Donohoe, Gary ; Morris, Derek ; Corvin, Aiden ; Gill, Michael ; Hariri, Ahmad ; Weinberger, Daniel R. ; Pendleton, Neil ; Iwata, Nakao ; Darvasi, Ariel ; Bitsios, Panos ; Rujescu, Dan ; Lahti, Jari ; Le Hellard, Stephanie ; Keller, Matthew C. ; Andreassen, Ole A. ; Deary, Ian J. ; Glahn, David C. ; Malhotra, Anil K. / Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2015 ; Vol. 168, No. 5. pp. 363-373.
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Trampush, JW, Lencz, T, Knowles, E, Davies, G, Guha, S, Pe'er, I, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, Mukherjee, S, Derosse, P, Lundervold, A, Steen, VM, John, M, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Ikeda, M, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Horan, M, Scult, M, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, A, Weinberger, DR, Pendleton, N, Iwata, N, Darvasi, A, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC & Malhotra, AK 2015, 'Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 168, no. 5, pp. 363-373. https://doi.org/10.1002/ajmg.b.32319

Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment. / Trampush, Joey W.; Lencz, Todd; Knowles, Emma; Davies, Gail; Guha, Saurav; Pe'er, Itsik; Liewald, David C.; Starr, John M.; Djurovic, Srdjan; Melle, Ingrid; Sundet, Kjetil; Christoforou, Andrea; Reinvang, Ivar; Mukherjee, Semanti; Derosse, Pamela; Lundervold, Astri; Steen, Vidar M.; John, Majnu; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G.; Giegling, Ina; Konte, Bettina; Ikeda, Masashi; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E.; Payton, Antony; Ollier, William; Horan, Mike; Scult, Matthew; Dickinson, Dwight; Straub, Richard E.; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill, Michael; Hariri, Ahmad; Weinberger, Daniel R.; Pendleton, Neil; Iwata, Nakao; Darvasi, Ariel; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C.; Andreassen, Ole A.; Deary, Ian J.; Glahn, David C.; Malhotra, Anil K.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 168, No. 5, 01.07.2015, p. 363-373.

Research output: Contribution to journalArticle

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.

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.

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