Exome arrays capture polygenic rare variant contributions to schizophrenia

Human Molecular Genetics

Volumn 25, Issue 5, 2016, Pages 1001-1007

  Richards, A L ^a   Leonenko, G ^a   Walters, J T ^a   Kavanagh, D H ^a,b   Rees, E G ^a   Evans, A ^a   Chambert, K D ^c   Moran, J L ^c   Goldstein, J ^c   Neale, B M ^c,d   McCarroll, S A ^c   Pocklington, A J ^a   Holmans, P A ^a   Owen, M J ^a   O'Donovan, M C ^a  

^a CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLELE; ARTICLE; CONTROLLED STUDY; EXOME; GENE FREQUENCY; GENE FUNCTION; GENE LOCUS; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; MAJOR CLINICAL STUDY; PRIORITY JOURNAL; SCHIZOPHRENIA; SIGNAL NOISE RATIO; UNITED KINGDOM; CASE CONTROL STUDY; COPY NUMBER VARIATION; DNA MICROARRAY; FEMALE; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; MALE; PATHOLOGY; QUANTITATIVE TRAIT; QUANTITATIVE TRAIT LOCUS; SAMPLE SIZE; SINGLE NUCLEOTIDE POLYMORPHISM;

NERVE PROTEIN; PROTEIN; WDR88 PROTEIN, HUMAN;

ALLELES; CASE-CONTROL STUDIES; DNA COPY NUMBER VARIATIONS; EXOME; FEMALE; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MALE; NERVE TISSUE PROTEINS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEINS; QUANTITATIVE TRAIT LOCI; QUANTITATIVE TRAIT, HERITABLE; SAMPLE SIZE; SCHIZOPHRENIA;

EID: 84962840928     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv620     Document Type: Article

References (44)

1. Gottesman, I.I. and Shields, J. (1967) A polygenic theory of schizophrenia. Proc. Natl Acad. Sci. USA, 58, 199-205.
2. Cardno, A.G. and Gottesman, I.I. (2000) Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am. J. Med. Genet., 97, 12-17.
3. International Schizophrenia, C., Purcell, S.M., Wray, N.R., Stone, J.L., Visscher, P.M., O'Donovan, M.C., Sullivan, P.F. and Sklar, P. (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 460, 748-752.
4. Sullivan, P.F., Daly, M.J. and O'Donovan, M. (2012) Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat. Rev. Genet., 13, 537-551.
5. SchizophreniaWorking Group of the Psychiatric Genomics, C. (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511, 421-427.
6. Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J.L., Kahler, A.K., Akterin, S., Bergen, S.E., Collins, A.L., Crowley, J.J., Fromer, M. et al. (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat. Genet., 45, 1150-1159.
7. Sebat, J., Levy, D.L. and McCarthy, S.E. (2009) Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders. Trends Genet., 25, 528-535.
8. Rees, E., Walters, J.T., Georgieva, L., Isles, A.R., Chambert, K.D., Richards, A.L., Mahoney-Davies, G., Legge, S.E., Moran, J.L., McCarroll, S.A. et al. (2014) Analysis of copy number variations at 15 schizophrenia-associated loci. Br. J. Psychiatry., 204, 108-114.
9. Richards, A.L., Jones, L., Moskvina, V., Kirov, G., Gejman, P.V., Levinson, D.F. and Sanders, A.R., Molecular Genetics of Schizophrenia, C., International Schizophrenia, C., Purcell, S. et al. (2012) Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain. Mol. Psychiatry, 17, 193-201.
10. Fromer, M., Pocklington, A.J., Kavanagh, D.H., Williams, H.J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D.M. et al. (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature, 506, 179-184.
11. Purcell, S.M., Moran, J.L., Fromer, M., Ruderfer, D., Solovieff, N., Roussos, P., O'Dushlaine, C., Chambert, K., Bergen, S.E., Kahler, A. et al. (2014) A polygenic burden of rare disruptive mutations in schizophrenia. Nature, 506, 185-190.
12. Kirov, G., Pocklington, A.J., Holmans, P., Ivanov, D., Ikeda, M., Ruderfer, D., Moran, J., Chambert, K., Toncheva, D., Georgieva, L. et al. (2012) De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol. Psychiatry, 17, 142-153.
13. Darnell, J.C., Van Driesche, S.J., Zhang, C., Hung, K.Y., Mele, A., Fraser, C.E., Stone, E.F., Chen, C., Fak, J.J., Chi, S.W. et al. (2011) FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell, 146, 247-261.
14. Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T. et al. (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet., 25, 25-29.
15. Gene Ontology, C. (2015) Gene Ontology Consortium: going forward. Nucleic Acids Res., 43, D1049-D1056.
16. Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M. and Tanabe, M. (2014) Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res., 42, D199-D205.
17. Kanehisa, M. and Goto, S. (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res., 28, 27-30.
18. Schaefer, C.F., Anthony, K., Krupa, S., Buchoff, J., Day, M., Hannay, T. and Buetow, K.H. (2009) PID: the pathway interaction database. Nucleic Acids Res., 37, D674-D679.
19. Eppig, J.T., Blake, J.A., Bult, C.J., Kadin, J.A. and Richardson, J.E., Mouse Genome Database, G. (2015) The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease. Nucleic Acids Res., 43, D726-D736.
20. Nishimura, D. (2004) Biotech software & internet report. Biocarta, 2, 117-120.
21. Mi, H., Muruganujan, A. and Thomas, P.D. (2013) PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees. Nucleic Acids Res., 41, D377-D386.
22. Mi, H., Muruganujan, A., Casagrande, J.T. and Thomas, P.D. (2013) Large-scale gene function analysis with the PANTHER classification system. Nat. Protoc., 8, 1551-1566.
23. Croft, D., Mundo, A.F., Haw, R., Milacic, M., Weiser, J., Wu, G., Caudy, M., Garapati, P., Gillespie, M., Kamdar, M.R. et al. (2014) The Reactome pathway knowledgebase. Nucleic Acids Res., 42, D472-D477.
24. Milacic, M., Haw, R., Rothfels, K., Wu, G., Croft, D., Hermjakob, H., D'Eustachio, P. and Stein, L. (2012) Annotating cancer variants and anti-cancer therapeutics in Reactome. Cancers, 4, 1180-1211.
25. Zuk, O., Schaffner, S.F., Samocha, K., Do, R., Hechter, E., Kathiresan, S., Daly, M.J., Neale, B.M., Sunyaev, S.R. and Lander, E.S. (2014) Searching for missing heritability: designing rare variant association studies. Proc. Natl Acad. Sci. USA, 111, E455-E464.
26. Kirov, G., Rees, E., Walters, J.T., Escott-Price, V., Georgieva, L., Richards, A.L., Chambert, K.D., Davies, G., Legge, S.E., Moran, J.L. et al. (2014) The penetrance of copy number variations for schizophrenia and developmental delay. Biol. Psychiatry, 75, 378-385.
27. Gusev, A., Lee, S.H., Trynka, G., Finucane, H., Vilhjalmsson, B.J., Xu, H., Zang, C., Ripke, S., Bulik-Sullivan, B., Stahl, E. et al. (2014) Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am. J. Hum. Genet., 95, 535-552.
28. Xu, B., Ionita-Laza, I., Roos, J.L., Boone, B., Woodrick, S., Sun, Y., Levy, S., Gogos, J.A. and Karayiorgou, M. (2012) De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat. Genet., 44, 1365-1369.
29. Gulsuner, S., Walsh, T., Watts, A.C., Lee, M.K., Thornton, A.M., Casadei, S., Rippey, C. and Shahin, H., Consortium on the Genetics of, S., Group, P.S. et al. (2013) Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell, 154, 518-529.
30. Girard, S.L., Gauthier, J., Noreau, A., Xiong, L., Zhou, S., Jouan, L., Dionne-Laporte, A., Spiegelman, D., Henrion, E., Diallo, O. et al. (2011) Increased exonic de novo mutation rate in individuals with schizophrenia. Nat. Genet., 43, 860-863.
31. Hamshere, M.L., Walters, J.T., Smith, R., Richards, A.L., Green, E., Grozeva, D., Jones, I., Forty, L., Jones, L., Gordon-Smith, K. et al. (2013) Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC. Mol. Psychiatry, 18, 708-712.
32. Carroll, L.S., Williams, H.J., Walters, J., Kirov, G., O'Donovan, M.C. andOwen, M.J. (2011) Mutation screening of the 3q29 microdeletion syndrome candidate genes DLG1 and PAK2 in schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet., 156B, 844-849.
33. Wing, J.K., Babor, T., Brugha, T., Burke, J., Cooper, J.E., Giel, R., Jablenski, A., Regier, D. and Sartorius, N. (1990) Scan-schedules for clinical-assessment in neuropsychiatry. Arch. Gen. Psychiatry, 47, 589-593.
34. American Psychiatric Association. (1994) Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). American Psychiatric Association, Washington, DC.
35. Power, C. and Elliott, J. (2006) Cohort profile: 1958 British birth cohort (National Child Development Study). Int. J. Epidemiol., 35, 34-41.
36. Strachan, D.P., Rudnicka, A.R., Power, C., Shepherd, P., Fuller, E., Davis, A., Gibb, I., Kumari, M., Rumley, A., Macfarlane, G.J. et al. (2007) Lifecourse influences on health among British adults: Effects of region of residence in childhood and adulthood. Int. J. Epidemiol., 36, 522-531.
37. Wellcome Trust Case Control, C. (2007) Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature, 447, 661-678.
38. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J. et al. (2007) PLINK: a tool set forwhole-genome association and population-based linkage analyses. Am. J. Hum. Genet., 81, 559-575.
39. Illumina Inc. (2005) Illumina GenCall Data Analysis Software. Technology Spotlight
40. Patterson, N., Price, A.L. and Reich, D. (2006) Population structure and eigenanalysis. PLoS Genet., 2, e190.
41. Price, A.L., Patterson, N.J., Plenge, R.M., Weinblatt, M.E., Shadick, N.A. and Reich, D. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet., 38, 904-909.
42. Goldstein, J.I., Crenshaw, A., Carey, J., Grant, G.B., Maguire, J., Fromer, M., O'Dushlaine, C., Moran, J.L., Chambert, K., Stevens, C. et al. (2012) zCall: a rare variant caller for arraybased genotyping: genetics and population analysis. Bioinformatics, 28, 2543-2545.
43. Lee, S., Emond, M.J., Bamshad, M.J., Barnes, K.C., Rieder, M.J. and Nickerson, D.A., Team, N.G.E.S.P.-E.L.P., Christiani, D.C., Wurfel, M.M. and Lin, X. (2012) Optimal unified approach for rare-variant association testing with application to smallsample case-control whole-exome sequencing studies. Am. J. Hum. Genet., 91, 224-237.
44. Purcell, S., Cherny, S.S. and Sham, P.C. (2003) Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics, 19, 149-150.