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GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.
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Trampush, JW; Yang, MLZ; Yu, J; Knowles, E; Davies, G; Liewald, DC; Starr, JM; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I; DeRosse, P; Lundervold, AJ; Steen, VM; Espeseth, T; Räikkönen, K; Widen, E; Palotie, A; Eriksson, JG; Giegling, I; Konte, B; Roussos, P; Giakoumaki, S; Burdick, KE; Payton, A; Ollier, W; Horan, M; Chiba-Falek, O; Attix, DK; Need, AC; Cirulli, ET; Voineskos, AN; Stefanis, NC; Avramopoulos, D; Hatzimanolis, A; Arking, DE; Smyrnis, N; Bilder, RM; Freimer, NA; Cannon, TD; London, E; Poldrack, RA; Sabb, FW; Congdon, E; Conley, ED; Scult, MA; Dickinson, D; Straub, RE; Donohoe, G; Morris, D; Corvin, A; Gill, M; Hariri, AR; Weinberger, DR; Pendleton, N; Bitsios, P; Rujescu, D; Lahti, J; Le Hellard, S; Keller, MC; Andreassen, OA; Deary, IJ; Glahn, DC; Malhotra, AK; Lencz, T
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In: Molecular psychiatry, vol 22, iss 3 (2017)
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Abstract:
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 (~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<5 × 10-8). 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.
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Keyword:
Adult; Alleles; Biological Sciences; Cognition; European Continental Ancestry Group; Female; Gene Frequency; Genetic Association Studies; Genetic Loci; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Male; Medical and Health Sciences; Middle Aged; Multifactorial Inheritance; Neurocognitive Disorders; Polymorphism; Psychiatry; Psychology and Cognitive Sciences; Single Nucleotide
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URL: https://escholarship.org/uc/item/2qj7x9fw
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| 2 |
GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium
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A Community-Academic Partnered Grant Writing Series to Build Infrastructure for Partnered Research
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In: King, KM; Pardo, YJ; Norris, KC; Diaz-Romero, M; Morris, D; Vassar, SD; et al.(2015). A Community-Academic Partnered Grant Writing Series to Build Infrastructure for Partnered Research. Clinical and Translational Science, 8(5), 573 - 578. doi:10.1111/cts.12327. UCLA: Retrieved from: http://www.escholarship.org/uc/item/65g4k75x (2015)
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A Community-Academic Partnered Grant Writing Series to Build Infrastructure for Partnered Research
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In: King, KM; Pardo, YJ; Norris, KC; Diaz-Romero, M; Morris, D; Vassar, SD; et al.(2015). A Community-Academic Partnered Grant Writing Series to Build Infrastructure for Partnered Research. Clinical and Translational Science. doi:10.1111/cts.12327. UCLA: Retrieved from: http://www.escholarship.org/uc/item/3783j80n (2015)
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A Community-Academic Partnered Grant Writing Series to Build Infrastructure for Partnered Research
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In: Clinical and Translational Science, vol 8, iss 5 (2015)
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The Social Attribution Task-Multiple Choice (SAT-MC): A Psychometric and Equivalence Study of an Alternate Form
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Identification of vowel length, word stress, and compound words and phrases by postlingually deafened cochlear implant listeners.
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In: J Am Acad Audiol , 24 (9) 879 - 890. (2013) (2013)
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Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22
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Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22
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Language discrimination by human newborns and by cotton-top tamarin monkeys.
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In: ISSN: 0036-8075 ; EISSN: 1095-9203 ; Science ; https://hal.archives-ouvertes.fr/hal-00260029 ; Science, American Association for the Advancement of Science, 2000, 288 (5464), pp.349-51 (2000)
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Welsh Language Socialization within the Family
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In: http://www.iaith.eu/uploads/language_socialisation_in_the_family_dr_kathryn_jones_a_dr_delyth_morriscont._wales_2006.pdf
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