Identification of genetic loci jointly influencing schizophrenia risk and the cognitive traits of verbal-numerical reasoning, reaction time, and general cognitive function

JAMA Psychiatry

Volumn 74, Issue 10, 2017, Pages 1065-1075

  Smeland, Olav B ^a,b,c   Frei, Oleksandr ^a   Kauppi, Karolina ^c,d   Hill, W David ^e   Li, Wen ^a   Wang, Yunpeng ^a,c   Krull, Florian ^a   Bettella, Francesco ^a   Eriksen, Jon A ^a   Witoelar, Aree ^a   Davies, Gail ^e   Fan, Chun C ^c,f   Thompson, Wesley K ^c,g   Lam, Max ^h   Lencz, Todd ^i,j,k   Chen, Chi Hua ^c   Ueland, Torill ^a   Jönsson, Erik G ^a,b,l   Djurovic, Srdjan ^b,m   Deary, Ian J ^e   Dale, Anders M ^c,n   Andreassen, Ole A ^a,b   more..

^a UNIVERSITY OF OSLO   (Norway)

^b OSLO UNIVERSITY HOSPITAL   (Norway)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UMEÅ UNIVERSITY   (Sweden)

^e UNIVERSITY OF EDINBURGH   (United Kingdom)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g Institute of Biological Psychiatry MHC Sct Hans Mental Health Devices Copenhagen   (Denmark)

^h INSTITUTE OF MENTAL HEALTH   (Singapore)

ⁱ ZUCKER HILLSIDE HOSPITAL   (United States)

^j FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH   (United States)

^k DONALD AND BARBARA ZUCKER SCHOOL OF MEDICINE AT HOFSTRA NORTHWELL   (United States)

^l KAROLINSKA INSTITUTE   (Sweden)

^m UNIVERSITY OF BERGEN   (Norway)

ⁿ UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; ALPHA CATENIN; CTNNA2 PROTEIN, HUMAN; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; TBC1D5 PROTEIN, HUMAN;

ADULT; ALLELE; ARTICLE; BIOBANK; CHROMOSOME; CHROMOSOME 22Q13.2; COGNITION; COHORT ANALYSIS; GENE LOCUS; GENERAL COGNITIVE FUNCTION; GENETIC IDENTIFICATION; GENETIC TRAIT; GENETIC VARIABILITY; GENOME-WIDE ASSOCIATION STUDY; HUMAN; MAJOR CLINICAL STUDY; MOLECULAR GENETICS; QUANTITATIVE TRAIT LOCUS; REACTION TIME; SCHIZOPHRENIA; TASK PERFORMANCE; VERBAL NUMERICAL REASONING; COGNITIVE DYSFUNCTION; COMPLICATION; FEMALE; GENE LINKAGE DISEQUILIBRIUM; GENETIC VARIATION; GENETICS; MALE; PHYSIOLOGY; QUANTITATIVE TRAIT; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; ALPHA CATENIN; COGNITION; COGNITIVE DYSFUNCTION; FEMALE; GENETIC LOCI; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; GTPASE-ACTIVATING PROTEINS; HUMANS; LINKAGE DISEQUILIBRIUM; MALE; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT, HERITABLE; REACTION TIME; SCHIZOPHRENIA;

EID: 85030627618     PISSN: 2168622X     EISSN: None     Source Type: Journal    
DOI: 10.1001/jamapsychiatry.2017.1986     Document Type: Article

References (56)

1. Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382 (9904):1575-1586.
2. Green MF, Harvey PD. Cognition in schizophrenia: past, present, and future. Schizophr Res Cogn. 2014;1(1):e1-e9.
3. Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophr Bull. 2000;26(1):119-136.
4. Kahn RS, Keefe RS. Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry. 2013;70(10):1107-1112.
5. Dickinson D, Ragland JD, Gold JM, Gur RC. General and specific cognitive deficits in schizophrenia: Goliath defeats David? Biol Psychiatry. 2008;64(9):823-827.
6. Aas M, Dazzan P, Mondelli V, Melle I, Murray RM, Pariante CM. A systematic review of cognitive function in first-episode psychosis, including a discussion on childhood trauma, stress, and inflammation. Front Psychiatry. 2014;4:182.
7. Reichenberg A, Caspi A, Harrington H, et al. Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. Am J Psychiatry. 2010;167(2):160-169.
8. Fusar-Poli P, Deste G, Smieskova R, et al. Cognitive functioning in prodromal psychosis: a meta-analysis. Arch Gen Psychiatry. 2012;69(6):562-571.
9. Mohamed S, Rosenheck R, Swartz M, Stroup S, Lieberman JA, Keefe RS. Relationship of cognition and psychopathology to functional impairment in schizophrenia. Am J Psychiatry. 2008;165(8):978-987.
10. Keefe RS, Buchanan RW, Marder SR, et al. Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? Schizophr Bull. 2013;39(2):417-435.
11. Zai G, Robbins TW, Sahakian BJ, Kennedy JL. A review of molecular genetic studies of neurocognitive deficits in schizophrenia. Neurosci Biobehav Rev. 2017;72:50-67.
12. Keshavan MS, Kulkarni S, Bhojraj T, et al. Premorbid cognitive deficits in young relatives of schizophrenia patients. Front Hum Neurosci. 2010;3:62.
13. McIntosh AM, Harrison LK, Forrester K, Lawrie SM, Johnstone EC. Neuropsychological impairments in people with schizophrenia or bipolar disorder and their unaffected relatives. Br J Psychiatry. 2005;186:378-385.
14. Bora E, Lin A, Wood SJ, Yung AR, McGorry PD, Pantelis C. Cognitive deficits in youth with familial and clinical high risk to psychosis: a systematic review and meta-analysis. Acta Psychiatr Scand. 2014;130(1):1-15.
15. Toulopoulou T, Goldberg TE, Mesa IR, et al. Impaired intellect and memory: a missing link between genetic risk and schizophrenia? Arch Gen Psychiatry. 2010;67(9):905-913.
16. Fowler T, Zammit S, Owen MJ, Rasmussen F. A population-based study of shared genetic variation between premorbid IQ and psychosis among male twin pairs and sibling pairs from Sweden. Arch Gen Psychiatry. 2012;69(5):460-466.
17. McIntosh AM, Gow A, Luciano M, et al. Polygenic risk for schizophrenia is associated with cognitive change between childhood and old age. Biol Psychiatry. 2013;73(10):938-943.
18. Lencz T, Knowles E, Davies G, et al. Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics Consortium (COGENT). Mol Psychiatry. 2014;19(2):168-174.
19. Hubbard L, Tansey KE, Rai D, et al. Evidence of common genetic overlap between schizophrenia and cognition. Schizophr Bull. 2016;42(3):832-842.
20. Liebers DT, Pirooznia M, Seiffudin F, Musliner KL, Zandi PP, Goes FS. Polygenic risk of schizophrenia and cognition in a population-based survey of older adults. Schizophr Bull. 2016;42(4): 984-991.
21. Hatzimanolis A, Bhatnagar P, Moes A, et al. Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood. Am J Med Genet B Neuropsychiatr Genet. 2015;168B(5):392-401.
22. Hagenaars SP, Harris SE, Davies G, et al; METASTROKE Consortium, International Consortium for Blood Pressure GWAS; SpiroMeta Consortium; CHARGE Consortium Pulmonary Group, CHARGE Consortium Aging and Longevity Group. Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N = 112 151) and 24 GWAS consortia. Mol Psychiatry. 2016;21(11):1624-1632.
23. Hill WD, Davies G, Liewald DC, McIntosh AM, Deary IJ; CHARGE Cognitive Working Group. Age-dependent pleiotropy between general cognitive function and major psychiatric disorders. Biol Psychiatry. 2016;80(4):266-273.
24. Trampush JW, Yang ML, Yu J, et al. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium. Mol Psychiatry. 2017;22(3):336-345.
25. Ripke S, O’Dushlaine C, Chambert K, et al; Multicenter Genetic Studies of Schizophrenia Consortium; Psychosis Endophenotypes International Consortium; Wellcome Trust Case Control Consortium 2. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet. 2013;45(10):1150-1159.
26. Davies G, Armstrong N, Bis JC, et al; Generation Scotland. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N = 53 949). Mol Psychiatry. 2015;20 (2):183-192.
27. Davies G, Marioni RE, Liewald DC, et al. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N = 112 151). Mol Psychiatry. 2016;21(6): 758-767.
28. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421-427.
29. Liu JZ, Hov JR, Folseraas T, et al; UK-PSCSC Consortium; International PSC Study Group; International IBD Genetics Consortium. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nat Genet. 2013;45(6):670-675.
30. Schork AJ, Wang Y, Thompson WK, Dale AM, Andreassen OA. New statistical approaches exploit the polygenic architecture of schizophrenia—implications for the underlying neurobiology. Curr Opin Neurobiol. 2016;36:89-98.
31. Andreassen OA, Thompson WK, Dale AM. Boosting the power of schizophrenia genetics by leveraging new statistical tools. Schizophr Bull. 2014;40(1):13-17.
32. Andreassen OA, Thompson WK, Schork AJ, et al; Psychiatric Genomics Consortium (PGC); Bipolar Disorder and Schizophrenia Working Groups. Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate. PLoS Genet. 2013;9(4):e1003455.
33. Andreassen OA, Harbo HF, Wang Y, et al; Psychiatric Genomics Consortium (PGC) Bipolar Disorder and Schizophrenia Work Groups; International Multiple Sclerosis Genetics Consortium (IMSGC). Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: implications for immune-related gene loci. Mol Psychiatry. 2015;20(2):207-214.
34. Andreassen OA, Djurovic S, Thompson WK, et al; International Consortium for Blood Pressure GWAS; Diabetes Genetics Replication and Meta-analysis Consortium; Psychiatric Genomics Consortium Schizophrenia Working Group. Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular-disease risk factors. Am J Hum Genet. 2013;92(2):197-209.
35. Le Hellard S, Wang Y, Witoelar A, et al; Schizophrenia Working Group of the Psychiatric Genomics Consortium. Identification of gene loci that overlap between schizophrenia and educational attainment. Schizophr Bull. 2017;43(3): 654-664.
36. Desikan RS, Schork AJ, Wang Y, et al; Inflammation Working Group and International Genomics of Alzheimer’s Disease Project (IGAP) and DemGene Investigators. Polygenic overlap between c-reactive protein, plasma lipids, and alzheimer disease. Circulation. 2015;131(23):2061-2069.
37. Andreassen OA, Desikan RS, Wang Y, et al. Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms [published correction appears in PLoS One. 2015;10(5): e0128048]. PLoS One. 2015;10(4):e0123057.
38. Nichols T, Brett M, Andersson J, Wager T, Poline JB. Valid conjunction inference with the minimum statistic. Neuroimage. 2005;25(3):653-660.
39. Schwartzman A, Lin X. The effect of correlation in false discovery rate estimation. Biometrika. 2011; 98(1):199-214.
40. Kang HJ, Kawasawa YI, Cheng F, et al. Spatio-temporal transcriptome of the human brain. Nature. 2011;478(7370):483-489.
41. Trabzuni D, Ryten M, Walker R, et al. Quality control parameters on a large dataset of regionally dissected human control brains for whole genome expression studies. J Neurochem. 2011;119(2):275-282.
42. GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45(6): 580-585.
43. Pers TH, Karjalainen JM, Chan Y, et al; Genetic Investigation of ANthropometric Traits (GIANT) Consortium. Biological interpretation of genome-wide association studies using predicted gene functions. Nat Commun. 2015;6:5890.
44. Sniekers S, Stringer S, Watanabe K, et al. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence [published online May 22, 2017]. Nat Genet. doi:10.1038/ng.3869
45. Nardini M, Gnesutta N, Donati G, et al. Sequence-specific transcription factor NF-Y displays histone-like DNA binding and H2B-like ubiquitination. Cell. 2013;152(1-2):132-143.
46. Yamanaka T, Tosaki A, Kurosawa M, et al. NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin and p62 accumulation and endoplasmic reticulum disorganization. Nat Commun. 2014;5:3354.
47. Power RA, Steinberg S, Bjornsdottir G, et al. Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nat Neurosci. 2015;18(7): 953-955.
48. Palmer BW, Heaton RK, Paulsen JS, et al. Is it possible to be schizophrenic yet neuropsychologically normal?Neuropsychology. 1997;11(3):437-446.
49. Babbs C, Lloyd D, Pagnamenta AT, et al; International Molecular Genetic Study of Autism Consortium (IMGSAC). De novo and rare inherited mutations implicate the transcriptional coregulator TCF20/SPBP in autism spectrum disorder. J Med Genet. 2014;51(11):737-747.
50. Clark NE, Garman SC. The 1.9 Å structure of human α-N-acetylgalactosaminidase: the molecular basis of Schindler and Kanzaki diseases. J Mol Biol. 2009;393(2):435-447.
51. Ferguson CS, Tyndale RF. Cytochrome P450 enzymes in the brain: emerging evidence of biological significance. Trends Pharmacol Sci. 2011; 32(12):708-714.
52. Schyman P, Lai W, Chen H, Wang Y, Shaik S. The directive of the protein: how does cytochrome P450 select the mechanism of dopamine formation? J Am Chem Soc. 2011;133(20):7977-7984.
53. Devor A, Andreassen OA, Wang Y, et al. Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia. Mol Psychiatry. 2017;22(6):792-801.
54. Zhang Q, Shen Q, Xu Z, et al. The effects of CACNA1C gene polymorphism on spatial working memory in both healthy controls and patients with schizophrenia or bipolar disorder. Neuropsychopharmacology. 2012;37(3):677-684.
55. Dietsche B, Backes H, Laneri D, et al. The impact of a CACNA1C gene polymorphism on learning and hippocampal formation in healthy individuals: a diffusion tensor imaging study. Neuroimage. 2014;89:256-261.
56. Solovieff N, Cotsapas C, Lee PH, Purcell SM, Smoller JW. Pleiotropy in complex traits: challenges and strategies. Nat Rev Genet. 2013;14(7):483-495.