BACKGROUND: Several aspects of neurocognitive function have high heritability, but the molecular genetic mechanisms underlying neurocognition are not known. We performed a genome-wide association study (GWAS) to identify genes associated with neurocognition. METHODS: 700 Subjects (schizophrenia spectrum disorder, n=190, bipolar disorder n=157 and healthy individuals n=353) were tested with an extensive neuropsychological test battery, and genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0. After quality control, linear regression analysis of each of the 24 cognitive tests on the SNP dosage was performed, including age, gender, education and disease group as covariates. Additionally, 9 SNPs trending toward genome-wide significance were considered for epistatic interactions. RESULTS: Four SNPs and 2 independent association signals achieving genome-wide significance were identified. Three intronic SNPs in PTPRO were associated with learning and memory (CVLT-II LDFR) (rs17222089, p=1.55×10(-8); rs11056571, p=1.68×10(-8); and rs2300290, p=1.09×10(-8)). rs719714 downstream of WDR72 was associated with executive functioning (CW-3: Inhibition, D-KEFS) (p=4.32×10(-8)). A highly significant epistatic interaction was found between rs9378605 upstream of FOXQ1 and rs11699311 downstream of SUMO1P1 for the Grooved Pegboard test (p=7.6×10(-14)). CONCLUSIONS: We identified four novel loci associated with neurocognitive function and one novel epistatic interaction. The findings should be replicated in independent samples, but indicate a role of PTPRO in learning and memory, WDR72 with executive functioning, and an interaction between FOXQ1 and SUMO1P1 for psychomotor speed.
BACKGROUND: Several aspects of neurocognitive function have high heritability, but the molecular genetic mechanisms underlying neurocognition are not known. We performed a genome-wide association study (GWAS) to identify genes associated with neurocognition. METHODS: 700 Subjects (schizophrenia spectrum disorder, n=190, bipolar disorder n=157 and healthy individuals n=353) were tested with an extensive neuropsychological test battery, and genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0. After quality control, linear regression analysis of each of the 24 cognitive tests on the SNP dosage was performed, including age, gender, education and disease group as covariates. Additionally, 9 SNPs trending toward genome-wide significance were considered for epistatic interactions. RESULTS: Four SNPs and 2 independent association signals achieving genome-wide significance were identified. Three intronic SNPs in PTPRO were associated with learning and memory (CVLT-II LDFR) (rs17222089, p=1.55×10(-8); rs11056571, p=1.68×10(-8); and rs2300290, p=1.09×10(-8)). rs719714 downstream of WDR72 was associated with executive functioning (CW-3: Inhibition, D-KEFS) (p=4.32×10(-8)). A highly significant epistatic interaction was found between rs9378605 upstream of FOXQ1 and rs11699311 downstream of SUMO1P1 for the Grooved Pegboard test (p=7.6×10(-14)). CONCLUSIONS: We identified four novel loci associated with neurocognitive function and one novel epistatic interaction. The findings should be replicated in independent samples, but indicate a role of PTPRO in learning and memory, WDR72 with executive functioning, and an interaction between FOXQ1 and SUMO1P1 for psychomotor speed.
Authors: Monica D Hartanti; Roseanne Rosario; Katja Hummitzsch; Nicole A Bastian; Nicholas Hatzirodos; Wendy M Bonner; Rosemary A Bayne; Helen F Irving-Rodgers; Richard A Anderson; Raymond J Rodgers Journal: PLoS One Date: 2020-02-20 Impact factor: 3.240
Authors: H Zhang; M Koruyucu; F Seymen; Y Kasimoglu; J-W Kim; S Tinawi; C Zhang; M L Jacquemont; A R Vieira; J P Simmer; J C C Hu Journal: J Dent Res Date: 2019-02-19 Impact factor: 6.116
Authors: N Akula; J Barb; X Jiang; J R Wendland; K H Choi; S K Sen; L Hou; D T W Chen; G Laje; K Johnson; B K Lipska; J E Kleinman; H Corrada-Bravo; S Detera-Wadleigh; P J Munson; F J McMahon Journal: Mol Psychiatry Date: 2014-01-07 Impact factor: 15.992
Authors: D A Bennett; I J Deary; M A Ikram; L J Launer; A L Fitzpatrick; S Seshadri; C M van Duijn; T H Mosley; C A Ibrahim-Verbaas; J Bressler; S Debette; M Schuur; A V Smith; J C Bis; G Davies; S Trompet; J A Smith; C Wolf; L B Chibnik; Y Liu; V Vitart; M Kirin; K Petrovic; O Polasek; L Zgaga; C Fawns-Ritchie; P Hoffmann; J Karjalainen; J Lahti; D J Llewellyn; C O Schmidt; K A Mather; V Chouraki; Q Sun; S M Resnick; L M Rose; C Oldmeadow; M Stewart; B H Smith; V Gudnason; Q Yang; S S Mirza; J W Jukema; P L deJager; T B Harris; D C Liewald; N Amin; L H Coker; O Stegle; O L Lopez; R Schmidt; A Teumer; I Ford; N Karbalai; J T Becker; M K Jonsdottir; R Au; Rsn Fehrmann; S Herms; M Nalls; W Zhao; S T Turner; K Yaffe; K Lohman; J C van Swieten; Slr Kardia; D S Knopman; W M Meeks; G Heiss; E G Holliday; P W Schofield; T Tanaka; D J Stott; J Wang; P Ridker; A J Gow; A Pattie; J M Starr; L J Hocking; N J Armstrong; S McLachlan; J M Shulman; L C Pilling; G Eiriksdottir; R J Scott; N A Kochan; A Palotie; Y-C Hsieh; J G Eriksson; A Penman; R F Gottesman; B A Oostra; L Yu; A L DeStefano; A Beiser; M Garcia; J I Rotter; M M Nöthen; A Hofman; P E Slagboom; Rgj Westendorp; B M Buckley; P A Wolf; A G Uitterlinden; B M Psaty; H J Grabe; S Bandinelli; D I Chasman; F Grodstein; K Räikkönen; J-C Lambert; D J Porteous; J F Price; P S Sachdev; L Ferrucci; J R Attia; I Rudan; C Hayward; A F Wright; J F Wilson; S Cichon; L Franke; H Schmidt; J Ding; Ajm de Craen; M Fornage Journal: Mol Psychiatry Date: 2015-04-14 Impact factor: 15.992
Authors: A J Schork; T T Brown; D J Hagler; W K Thompson; C-H Chen; A M Dale; T L Jernigan; N Akshoomoff Journal: Genes Brain Behav Date: 2018-05-10 Impact factor: 3.449
Authors: Gabriëlla A M Blokland; Angus K Wallace; Narelle K Hansell; Paul M Thompson; Ian B Hickie; Grant W Montgomery; Nicholas G Martin; Katie L McMahon; Greig I de Zubicaray; Margaret J Wright Journal: Int J Psychophysiol Date: 2016-09-23 Impact factor: 2.997