Search

Your search keyword '"Wildenauer, Db"' showing total 10 results
Start Over Author "Wildenauer, Db" Topic polymorphism, single nucleotide
10 results on '"Wildenauer, Db"'

1. Comparative genetic architectures of schizophrenia in East Asian and European populations.

Author

Lam M, Chen CY, Li Z, Martin AR, Bryois J, Ma X, Gaspar H, Ikeda M, Benyamin B, Brown BC, Liu R, Zhou W, Guan L, Kamatani Y, Kim SW, Kubo M, Kusumawardhani AAAA, Liu CM, Ma H, Periyasamy S, Takahashi A, Xu Z, Yu H, Zhu F, Chen WJ, Faraone S, Glatt SJ, He L, Hyman SE, Hwu HG, McCarroll SA, Neale BM, Sklar P, Wildenauer DB, Yu X, Zhang D, Mowry BJ, Lee J, Holmans P, Xu S, Sullivan PF, Ripke S, O'Donovan MC, Daly MJ, Qin S, Sham P, Iwata N, Hong KS, Schwab SG, Yue W, Tsuang M, Liu J, Ma X, Kahn RS, Shi Y, and Huang H

Subjects
Case-Control Studies, Asia, Eastern, Genetics, Population, Genome-Wide Association Study, Humans, Asian People genetics, Polymorphism, Single Nucleotide, Schizophrenia genetics, White People genetics
Abstract

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.

Published
2019
Full Text
View/download PDF

2. Association of rs1344706 in the ZNF804A gene with schizophrenia in a case/control sample from Indonesia.

Author

Schwab SG, Kusumawardhani AAAA, Dai N, Qin W, Wildenauer MDB, Agiananda F, Amir N, Antoni R, Arsianti T, Asmarahadi A, Diatri H, Djatmiko P, Irmansyah I, Khalimah S, Kusumadewi I, Kusumaningrum P, Lukman PR, Mustar L, Nasrun MW, Naswati S, Prasetiyawan P, Semen GM, Siste K, Tobing H, Widiasih N, Wiguna T, Wulandari WD, Benyamin B, and Wildenauer DB

Subjects
Adult, Case-Control Studies, Female, Genome-Wide Association Study, Genotype, Humans, Indonesia, Linkage Disequilibrium, Male, Genetic Predisposition to Disease genetics, Kruppel-Like Transcription Factors genetics, Polymorphism, Single Nucleotide genetics, Schizophrenia genetics
Abstract

Background: Association of rs1344706 in the ZNF804A gene (2q32.1) with schizophrenia was first reported in a genome wide scan conducted in a sample of 479 cases and replicated in 6666 cases. Subsequently, evidence by replication was obtained in several samples with European- and Asian ancestral background., Methods: We report ascertainment, clinical characterization, quality control, and determination of ancestral background of a case control sample from Indonesia, comprising 1067 cases and 1111 ancestry matched controls. Genotyping was performed using a fluorescence-based allelic discrimination assay (TaqMan SNP genotyping assay) and a newly designed PCR-RFLP assay for confirmation of rs1344706 genotypes., Results: We confirmed association of the T-allele of rs1344706 with schizophrenia in a newly ascertained sample from Indonesia with Southeast Asian ancestral background (P=0.019, OR=1.155, 95%, CI 1.025-1.301). In addition, we studied several SNPs in the vicinity of rs1344706, for which nominally significant results had been reported. None of the association P values of the additional SNPs exceeded that of rs1344706., Conclusion: We provide additional evidence for association of the ZNF804A gene with schizophrenia. We conclude that rs1344706 or a yet unknown polymorphism in linkage disequilibrium is also involved in conferring susceptibility to schizophrenia in samples with different (Asian) ancestral backgrounds., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Published
2013
Full Text
View/download PDF

3. A family-based association study of DNA sequence variants in GRM7 with schizophrenia in an Indonesian population.

Author

Ganda C, Schwab SG, Amir N, Heriani H, Irmansyah I, Kusumawardhani A, Nasrun M, Widyawati I, Maier W, and Wildenauer DB

Subjects
DNA Mutational Analysis, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, Humans, Indonesia, Introns, Linkage Disequilibrium, Pedigree, Schizophrenia ethnology, Asian People genetics, Chromosomes, Human, Pair 3, Polymorphism, Single Nucleotide, Receptors, Metabotropic Glutamate genetics, Schizophrenia genetics
Abstract

We previously reported genome-wide significant linkage to chromosome 3p in a sib-pair family sample from Indonesia. A promising candidate gene within the linked region is the metabotropic glutamate receptor subtype 7 (GRM7), involved in glutamatergic neurotransmission. We genotyped 18 single nucleotide polymorphisms in GRM7 in the sample of 124 Indonesian sib-pair families that had provided the significant linkage finding. Transmission disequilibrium analysis revealed nominally significant transmission distortion of rs17031835 in intron 1 of GRM7 (p=0.004, before correction for multiple testing), along with haplotypes containing rs17031835. No other single marker was found to be significantly associated with schizophrenia in our sample. The results from our study provide support for the idea that glutamatergic neurotransmission and specifically the GRM7 gene might be relevant to the development of schizophrenia. Further studies supporting this finding are warranted.

Published
2009
Full Text
View/download PDF

4. Association of PIP5K2A with schizophrenia: a study in an indonesian family sample.

Author

Saggers-Gray L, Heriani H, Handoko HY, Irmansyah I, Kusumawardhani AA, Widyawati I, Amir N, Nasrun MW, Schwab SG, and Wildenauer DB

Subjects
Asian People genetics, Family Health, Genetic Markers, Haplotypes, Humans, Indonesia epidemiology, Siblings, Genetic Predisposition to Disease genetics, Phosphotransferases (Alcohol Group Acceptor) genetics, Polymorphism, Single Nucleotide, Schizophrenia genetics
Abstract

PIP5K2A variants have been shown to be associated with schizophrenia in Caucasian populations. This study tested 12 PIP5K2A SNPs for association with schizophrenia in a sample of 152 sib-pair families of Indonesian descent. All SNPs had previously been tested for association with schizophrenia in a German family sample by Schwab et al. [2006; Mol Psychiatry] and seven SNPs were nominally associated with schizophrenia in this previous study. The purpose of the study was to examine whether previously implicated PIP5K2A variants influence susceptibility to schizophrenia in populations of non-European descent. No single markers showed nominal association with schizophrenia in this Indonesian family sample, however multi-marker haplotypes including a previously associated exonic SNP marker revealed nominally significant association (P = 0.03). Power to detect association was greater than 80% for all previously implicated variants except for rs11013052, where power was greatly reduced due to the low minor allele frequency of this marker in the Indonesian sample. An explorative study combining the results of this study with those of our previous study indicated that rs11013052 was significantly associated with schizophrenia in the combined sample (P = 0.002). The results of this study suggest that any contribution of previously implicated DNA variants within the PIP5K2A gene to schizophrenia susceptibility in the Indonesian population is only minor.

Published
2008
Full Text
View/download PDF

5. Evaluation of association of SNPs in the TNF alpha gene region with schizophrenia.

Author

Morar B, Schwab SG, Albus M, Maier W, Lerer B, and Wildenauer DB

Subjects
Family, Gene Frequency, Genes, MHC Class I, Genetic Markers, Haplotypes, Humans, Polymorphism, Restriction Fragment Length, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Schizophrenia genetics, Tumor Necrosis Factor-alpha genetics
Abstract

The association of the tumor necrosis factor alpha (TNFalpha) -G308A promoter polymorphism with schizophrenia has complemented clinical findings of increased levels of the TNFalpha cytokine in schizophrenic patients, with some support for a functional consequence of the variant. Our previous studies of genetic causes in schizophrenia supported findings of linkage to the major histocompatibility complex (MHC) region where the TNFalpha gene is located as well as association with the -G308A promoter polymorphism. While the common G-allele shows association in our sample, association with the A-allele has been reported by other groups. This suggests linkage disequilibrium (LD) rather than direct involvement in the disorder. In order to define LD of DNA variants with the disorder in this area, we analyzed 36 SNPs in a 165-kb region around this polymorphism. We detected nominally significant associations (P < 0.05) of three markers (including the -G308A promoter polymorphism) and multiple haplotypes with schizophrenia in our sample of 204 families (79 sib-pairs and 125 trios). The association is largely restricted to a 30 kb high LD region/block and should assist in the identification of a schizophrenia susceptibility gene within the block or elsewhere in the MHC., ((c) 2006 Wiley-Liss, Inc.)

Published
2007
Full Text
View/download PDF

6. Homozygosity of the interleukin-10 receptor 1 G330R allele is associated with schizophrenia.

Author

Schosser A, Aschauer HN, Wildenauer DB, Schwab SG, Albus M, Maier W, Schloegelhofer M, Leisch F, Hornik K, Murray SS, and Gasche C

Subjects
Alleles, Arginine genetics, Case-Control Studies, Female, Gene Frequency, Genetic Linkage, Genotype, Glycine genetics, Humans, Male, Models, Genetic, Homozygote, Interleukin-10 Receptor alpha Subunit genetics, Polymorphism, Single Nucleotide, Schizophrenia genetics
Abstract

Infections of unknown origin and an altered immune response have been hypothesized to play a role in the pathogenesis of schizophrenia. We have previously identified two single nucleotide polymorphisms (SNPs) of the IL-10 receptor 1 (IL-10R1) causing a substitution of glycine 330 to arginine (G330R) and of serine 138 to glycine (S138G). A possible association between these IL-10R1 variants and schizophrenia has been investigated in the present study. DNA of 101 unrelated Austrian patients with a DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) consensus diagnosis of schizophrenia (n = 70) or schizoaffective disorder (n = 31) and DNA of 121 German schizophrenic patients (DSM-III-R) was analyzed for the presence of S138G and G330R by allele-specific multiplex PCRs. Data from patients were compared with 250 unrelated, psychiatric healthy controls. No difference in allele frequency was detected between patients and controls (G330R: 34.0% vs. 30.0%, P = 0.208; S138G: 19.7% vs. 16.6%, P = 0.235; by Fisher's exact test). However, there was a significant difference in genotype distribution (wt/wt, wt/mut, mut/mut) for G330R between patients (46.8%, 38.3%, 14.9%) and controls (47.6%, 44.8%, 7.6%; Fisher's test P = 0.032). No such difference was seen for S138G. Our results suggest that homozygosity of the IL-10R1 G330R allele is associated with schizophrenia and may contribute to the expression of disease phenotype in susceptible individuals., ((c) 2006 Wiley-Liss, Inc.)

Published
2007
Full Text
View/download PDF

7. Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

Author

Bigdeli, T. B, Ripke, S, Bacanu, Sa, Lee, S. H, Wray, Nr, Gejman, P. V, Rietschel, M, Cichon, S, St Clair, D, Corvin, A, Kirov, G, Mcquillin, A, Gurling, H, Rujescu, D, Andreassen, O. A, Werge, T, Blackwood, D. H. R, Pato, C. N, Pato, M. T, Malhotra, A. K, O'Donovan, M. C, Kendler, K. S, Fanous, A. H, Neale, Bm, Walters, Jt, Farh, Kh, Holmans, Pa, Lee, P, Bulik Sullivan, B, Collier, Da, Huang, H, Pers, Th, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Begemann, M, Belliveau, Ra, Bene, J, Bergen, Se, Bevilacqua, E, Bigdeli, Tb, Black, Dw, Børglum, Ad, Bruggeman, R, Buccola, Ng, Buckner, Rl, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, Rm, Carr, Vj, Carrera, N, Catts, Sv, Chambert, Kd, Chan, Rc, Chen, Ry, Chen, Ey, Cheng, W, Cheung, Ef, Chong, Sa, Cloninger, C, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, Jj, Curtis, D, Davidson, M, Davis, Kl, Degenhardt, F, Del, Favero, J, Delisi, Le, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott Price, V, Essioux, L, Fanous, Ah, Farrell, Ms, Frank, J, Franke, L, Freedman, R, Freimer, Nb, Friedl, M, Friedman, Ji, Fromer, M, Genovese, G, Georgieva, L, Gershon, Es, Giegling, I, Giusti Rodríguez, P, Godard, S, Goldstein, Ji, Golimbet, V, Gopal, S, Gratten, J, Grove, J, Haan, De, L, Hammer, C, Hamshere, Ml, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, Am, Henskens, Fa, Herms, S, Hirschhorn, Jn, Hoffmann, P, Hofman, A, Hollegaard, Mv, Hougaard, Dm, Ikeda, M, Joa, I, Julìa, A, Kahn, Rs, Kalaydjieva, L, Karachanak Yankova, S, Karjalainen, J, Kavanagh, D, Keller, Mc, Kelly, Bj, Kennedy, Jl, Khrunin, A, Kim, Y, Klovins, J, Knowles, Ja, Konte, B, Kucinskas, V, Kucinskiene, Za, Kuzelova Ptackova, H, Kähler, Ak, Laurent, C, Keong, Jl, Lee, S, Legge, Se, Lerer, B, Li, M, Li, T, Liang, Ky, Lieberman, J, Limborska, S, Loughland, Cm, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, Pk, Maher, Bs, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, Mccarley, Rw, Mcdonald, C, Mcintosh, Am, Meier, S, Meijer, Cj, Melegh, B, Melle, I, Mesholam Gately, Ri, Metspalu, A, Michie, Pt, Milani, L, Milanova, V, Mokrab, Y, Morris, Dw, Mors, O, Mortensen, Pb, Murphy, Kc, Murray, Rm, Myin Germeys, I, Müller Myhsok, B, Nelis, M, Nenadic, I, Nertney, Da, Nestadt, G, Nicodemus, Kk, Nikitina Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, F, Sy, Oh, Olincy, A, Olsen, L, Jv, Os, Pantelis, C, Papadimitriou, Gn, Papiol, S, Parkhomenko, E, Pato, Mt, Paunio, T, Pejovic Milovancevic, M, Perkins, Do, Pietiläinen, O, Pimm, J, Pocklington, Aj, Powell, J, Price, A, Pulver, Ae, Purcell, Sm, Quested, D, Rasmussen, Hb, Reichenberg, A, Reimers, Ma, Richards, Al, Roffman, Jl, Roussos, P, Ruderfer, Dm, Salomaa, V, Sanders, Ar, Schall, U, Schubert, Cr, Schulze, Tg, Schwab, Sg, Scolnick, Em, Scott, Rj, Seidman, Lj, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, Jm, Sim, K, Slominsky, P, Smoller, Jw, Hc, So, Spencer, Cc, Stahl, Ea, Stefansson, H, Steinberg, S, Stogmann, E, Straub, Re, Strengman, E, Strohmaier, J, Stroup, T, Subramaniam, M, Suvisaari, J, Svrakic, Dm, Szatkiewicz, Jp, Söderman, E, Thirumalai, S, Toncheva, D, Tooney, Pa, Tosato, Sarah, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, Bt, Weiser, M, Wildenauer, Db, Williams, Nm, Williams, S, Witt, Sh, Wolen, Ar, Wong, Eh, Wormley, Bk, Jq, Wu, Hs, Xi, Zai, Cc, Zheng, X, Zimprich, F, Stefansson, K, Visscher, Pm, Adolfsson, R, Andreassen, Oa, Blackwood, Dh, Bramon, E, Buxbaum, Jd, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, Pv, Gill, M, Hultman, Cm, Iwata, N, Jablensky, Av, Jönsson, Eg, Kendler, Ks, Knight, J, Lencz, T, Levinson, Df, Qs, Li, Liu, J, Malhotra, Ak, Mccarroll, Sa, Moran, Jl, Mowry, Bj, Nöthen, Mm, Ophoff, Ra, Owen, Mj, Palotie, A, Pato, Cn, Petryshen, Tl, Posthuma, D, Riley, Bp, Sham, Pc, Sklar, P, Clair, Ds, Weinberger, Dr, Wendland, Jr, Daly, Mj, Sullivan, Pf, O'Donovan, Mc, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Bigdeli, Tim B, Ripke, Stephan, Bacanu, Silviu-Alin, Lee, Sang Hong, Fanous, Ayman H, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Psychosis Endophenotype International Consortium, Wellcome Trust Case-Control Consortium 2, Other departments, Adult Psychiatry, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and Del-Favero, Jurgen

Subjects
0301 basic medicine, Multifactorial Inheritance, Bipolar Disorder, Inheritance Patterns, Genome-wide association study, Single-nucleotide polymorphism, polygenic, heritability, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, Humans, SNP, GWAS, Family, Genetic Predisposition to Disease, Family history, Allele, Genetics (clinical), Genetic association, Genetics & Heredity, Psychiatry, Genetics, Depressive Disorder, Major, family history, Models, Genetic, Case-control study, medicine.disease, 3. Good health, schizophrenia, Psychiatry and Mental health, 030104 developmental biology, Schizophrenia, Case-Control Studies, Human medicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N=978), cases reporting no such family history (N=4,503), and unscreened controls (N=8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R-2=0.0021; P=0.00331; P-value threshold

Published
2016
Full Text
View/download PDF

8. Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway

Author

Nicodemus, Kk, Hargreaves, A, Morris, D, Anney, R, Gill, M, Corvin, A, Donohoe, G, Ripke, S, Sanders, Ar, Kendler, Ks, Levinson, Df, Sklar, P, Holmans, Pa, Lin, Dy, Duan, J, Ophoff, Ra, Andreassen, Oa, Scolnick, E, Cichon, S, Clair, St, D, Gurling, H, Werge, T, Rujescu, D, Blackwood, Dh, Pato, Cn, Malhotra, Ak, Purcell, S, Dudbridge, F, Neale, Bm, Rossin, L, Visscher, Pm, Posthuma, D, Ruderfer, Dm, Fanous, A, Stefansson, H, Steinberg, S, Mowry, Bj, Golimbet, V, Hert, De, M, Jönsson, Eg, Bitter, I, Pietiläinen, Op, Collier, Da, Tosato, Sarah, Agartz, I, Albus, M, Alexander, M, Amdur, Rl, Amin, F, Bass, N, Bergen, Se, Black, Dw, Børglum, Ad, Brown, Ma, Bruggeman, R, Buccola, Ng, Byerley, Wf, Cahn, W, Cantor, Rm, Carr, Vj, Catts, Sv, Choudhury, K, Cloninger, C, Cormican, P, Craddock, N, Danoy, Pa, Datta, S, Haan, De, L, Demontis, D, Dikeos, D, Djurovic, S, Donnelly, P, Duong, L, Dwyer, S, Fink Jensen, A, Freedman, R, Freimer, Nb, Friedl, M, Georgieva, L, Giegling, I, Glenthøj, B, Godard, S, Hamshere, M, Hansen, M, Hansen, T, Hartmann, Am, Henskens, Fa, Hougaard, Dm, Hultman, Cm, Ingason, A, Jablensky, Av, Jakobsen, Kd, Jay, M, Jürgens, G, Kahn, Rs, Keller, Mc, Kenis, G, Kenny, E, Kim, Y, Kirov, Gk, Konnerth, H, Konte, B, Krabbendam, L, Krasucki, R, Lasseter, Vk, Laurent, C, Lawrence, J, Lencz, T, Lerer, F, Liang, Ky, Lichtenstein, P, Lieberman, Ja, Linszen, Dh, Lönnqvist, J, Loughland, Cm, Maclean, Aw, Maher, Bs, Maier, W, Mallet, J, Malloy, P, Mattheisen, M, Mattingsdal, M, Mcghee, Ka, Mcgrath, Jj, Mcintosh, A, Mclean, De, Mcquillin, A, Melle, I, Michie, Pt, Milanova, V, Morris, Dw, Mors, O, Mortensen, Pb, Moskvina, V, Muglia, P, Myin Germeys, I, Nertney, Da, Nestadt, G, Nielsen, J, Nikolov, I, Nordentoft, M, Norton, N, Nöthen, Mm, O'Dushlaine, Ct, Olincy, A, Olsen, L, O'Neill, F, Ørntoft, Tf, Owen, Mj, Pantelis, C, Papadimitriou, G, Pato, Mt, Peltonen, L, Petursson, H, Pickard, B, Pimm, J, Pulver, Ae, Puri, V, Quested, D, Quinn, Em, Rasmussen, Hb, Réthelyi, Jm, Ribble, R, Rietschel, M, Riley, Bp, Ruggeri, Mirella, Schall, U, Schulze, Tg, Schwab, Sg, Scott, Rj, Shi, J, Sigurdsson, E, Silverman, Jm, Spencer, Cc, Stefansson, K, Strange, A, Strengman, E, Stroup, T, Suvisaari, J, Terenius, L, Thirumalai, S, Thygesen, Jh, Timm, S, Toncheva, D, Van, Den, Oord, E, Van, Os, Van, J, Winkel, R, Veldink, J, Walsh, D, Wang, Ag, Wiersma, D, Wildenauer, Db, Williams, Hj, Williams, Nm, Wormley, B, Zammit, S, Sullivan, Pf, O'Donovan, Mc, Daly, Mj, Gejman, P., Functional Genomics, Complex Trait Genetics, De Hert, Marc, Myin-Germeys, Inez, van Winkel, Ruud, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Amsterdam Neuroscience, and Adult Psychiatry

Subjects
epistasis, Male, Multifactorial Inheritance, polygenic, Neuropsychological Tests, involvement, 0302 clinical medicine, Neural Pathways, 2.1 Biological and endogenous factors, Psychology, schizophrenia risk, psychosis variant, Aetiology, 0303 health sciences, susceptibility gene znf804a, medicine.diagnostic_test, phenotypes, Zinc Fingers, Neuropsychological test, Single Nucleotide, Middle Aged, Serious Mental Illness, Psychiatry and Mental health, Memory, Short-Term, Mental Health, Schizophrenia, Major depressive disorder, Female, Cognitive Sciences, social and economic factors, Adult, medicine.medical_specialty, Psychosis, working memory, schizophrenia, IQ, Schizoaffective disorder, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Gene interaction, Genetic, Social cognition, Memory, Clinical Research, 2.3 Psychological, Behavioral and Social Science, medicine, Genetics, Humans, Genetic Predisposition to Disease, Bipolar disorder, Polymorphism, Psychiatry, 030304 developmental biology, Other Medical and Health Sciences, Prevention, Wellcome Trust Case Control Consortium 2, Neurosciences, Genetic Variation, Epistasis, Genetic, Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium, medicine.disease, attention, Brain Disorders, deficits, Short-Term, Psychotic Disorders, genome-wide association, Epistasis, healthy controls, identification, Cognition Disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

IMPORTANCE We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. OBJECTIVES To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. DESIGN, SETTING, AND PARTICIPANTS Patients with psychosis (n = 424)were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition.We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). MAIN OUTCOMES AND MEASURES Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. RESULTS Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1%to 3%of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2%using the polygenic score only to 4.8%(P = .11 and .001, respectively) but did not explain additional variation in control participants. CONCLUSIONS AND RELEVANCE These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score. © 2014 American Medical Association. All rights reserved.

Published
2014
Full Text
View/download PDF

9. Genetic schizophrenia risk variants jointly modulate total brain and white matter volume

Author

Terwisscha van Scheltinga, Af, Bakker, Sc, van Haren, Ne, Derks, Em, Buizer Voskamp, Je, Boos, Hb, Cahn, W, Hulshoff, Pol, Ripke, S, Ophoff, Ra, Kahn, Rs, Sanders, Ar, Kendler, Ks, Levinson, Df, Sklar, P, Holmans, Pa, Lin, Dy, Duan, J, Andreassen, Oa, Scolnick, E, Cichon, S, Clair, St, D, Corvin, A, Gurling, H, Werge, T, Rujescu, D, Blackwood, Dh, Pato, Cn, Malhotra, Ak, Purcell, S, Dudbridge, F, Neale, Bm, Rossin, L, Visscher, Pm, Posthuma, D, Ruderfer, Dm, Fanous, A, Stefansson, H, Steinberg, S, Mowry, Bj, Golimbet, V, Hert, De, M, Jonsson, Eg, Bitter, I, Pietiläinen, Op, Collier, Da, Tosato, Sarah, Agartz, I, Albus, M, Alexander, M, Amdur, Rl, Amin, F, Bass, N, Bergen, Se, Black, Dw, Børglum, Ad, Brown, Ma, Bruggeman, R, Buccola, Ng, Byerley, Wf, Cantor, Rm, Carr, Vj, Catts, Sv, Choudhury, K, Cloninger, C, Cormican, P, Craddock, N, Danoy, Pa, Datta, S, Haan, De, L, Demontis, D, Dikeos, D, Djurovic, S, Donnelly, P, Donohoe, G, Duong, L, Dwyer, S, Fink Jensen, A, Freedman, R, Freimer, Nb, Friedl, M, Georgieva, L, Giegline, I, Gill, M, Glenthøj, B, Godard, S, Hamshere, M, Hansen, M, Hansen, T, Hartmann, Am, Henskens, Fa, Hougaard, Dm, Hultman, Cm, Ingason, A, Jablensky, Av, Jakobsen, Kd, Jay, M, Jürgens, G, Keller, Mc, Kenis, G, Kenny, E, Kim, Y, Kirov, Gk, Konnerth, H, Konte, B, Krabbendam, L, Krasucki, R, Lasseter, Vk, Laurent, C, Lawrence, J, Lencz, T, Lerer, F, Liang, Ky, Lichtenstein, P, Lieberman, Ja, Linszen, Dh, Lönnqvist, J, Loughland, Cm, Maclean, Aw, Maher, Bs, Maier, W, Mallet, J, Malloy, P, Mattheisen, M, Mattingsdal, M, Mcghee, Ka, Mcgrath, Jj, Mcintosh, A, Mclean, De, Mcquillin, A, Melle, I, Michie, Pt, Milanova, V, Morris, Dw, Mors, O, Mortensen, Pb, Moskvina, V, Muglia, P, Myin Germeys, I, Nertney, Da, Nestadt, G, Nielsen, J, Nikolov, I, Nordentoft, M, Norton, N, Nöthen, Mm, O'Dushlaine, C, Olincy, A, Olsen, L, O'Neill, F, Ørntoft, Tf, Owen, Mj, Pantelis, C, Papadimitriou, G, Pato, Mt, Peltonen, L, Petursson, H, Pickard, B, Pimm, J, Pulver, Ae, Puri, V, Quested, D, Quinn, Em, Rasmussen, Hb, Réthelyi, Jm, Ribble, R, Rietschel, M, Riley, Bp, Ruggeri, Mirella, Schall, U, Schulze, Tg, Schwab, Sg, Scott, Rj, Shi, J, Sigurdsson, E, Silverman, Jm, Spencer, Cc, Stefansson, K, Strange, A, Strengman, E, Stroup, Ts, Suvisaari, J, Terenius, L, Thirumalai, S, Thygesen, Jh, Timm, S, Toncheva, D, van den Oord, E, van Os, J, Van, Winkel, R, Veldink, J, Walsh, D, Wang, Ag, Wiersma, D, Wildenauer, Db, Williams, Hj, Williams, Nm, Wormley, B, Zammit, S, Sullivan, Pf, O'Donovan, Mc, Daly, Mj, Gejman, Pv, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Adult Psychiatry, Functional Genomics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Myin-Germeys, Inez, De Hert, Marc, and van Winkel, Ruud

Subjects
Adult, Male, Psychosis, Genotype, Single-nucleotide polymorphism, Genome-wide association study, Biology, Nerve Fibers, Myelinated, Polymorphism, Single Nucleotide, Article, White matter, genome-wide, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, mental disorders, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Biological Psychiatry, structural MRI, Genetics, neuroimaging, Case-control study, Brain, imaging, medicine.disease, 030227 psychiatry, 3. Good health, schizophrenia, Endophenotype, Phenotype, medicine.anatomical_structure, psychiatric, Schizophrenia, Case-Control Studies, Female, endophenotype, Genome-Wide Association Study, SNPs, Atrophy, 030217 neurology & neurosurgery
Abstract

BACKGROUND: Thousands of common single nucleotide polymorphisms (SNPs) are weakly associated with schizophrenia. It is likely that subsets of disease-associated SNPs are associated with distinct heritable disease-associated phenotypes. Therefore, we examined the shared genetic susceptibility modulating schizophrenia and brain volume. METHODS: Odds ratios for genome-wide SNP data were calculated in the sample collected by the Psychiatric Genome-wide Association Study Consortium (8690 schizophrenia patients and 11,831 control subjects, excluding subjects from the present study). These were used to calculate individual polygenic schizophrenia (risk) scores in an independent sample of 152 schizophrenia patients and 142 healthy control subjects with available structural magnetic resonance imaging scans. RESULTS: In the entire group, the polygenic schizophrenia score was significantly associated with total brain volume (R2 = .048, p = 1.6 × 10(-4)) and white matter volume (R2 = .051, p = 8.6 × 10(-5)) equally in patients and control subjects. The number of (independent) SNPs that substantially influenced both disease risk and white matter (n = 2020) was much smaller than the entire set of SNPs that modulated disease status (n = 14,751). From the set of 2020 SNPs, a group of 186 SNPs showed most evidence for association with white matter volume and an explorative functional analysis showed that these SNPs were located in genes with neuronal functions. CONCLUSIONS: These results indicate that a relatively small subset of schizophrenia genetic risk variants is related to the (normal) development of white matter. This, in turn, suggests that disruptions in white matter growth increase the susceptibility to develop schizophrenia.

Published
2013
Full Text
View/download PDF

10. Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Author

Ripke, S, O'Dushlaine, C, Chambert, K, Moran, Jl, Kähler, Ak, Akterin, S, Bergen, Se, Collins, Al, Crowley, Jj, Fromer, M, Kim, Y, Lee, Sh, Magnusson, Pk, Sanchez, N, Stahl, Ea, Williams, S, Wray, Nr, Xia, K, Bettella, F, Borglum, Ad, Bulik Sullivan, Bk, Cormican, P, Craddock, N, Leeuw, De, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, Ml, Holmans, P, Hougaard, Dm, Kendler, Ks, Lin, K, Morris, Dw, Mors, O, Mortensen, Pb, Neale, Bm, O'Neill, Fa, Owen, Mj, Milovancevic, Mp, Posthuma, D, Powell, J, Richards, Al, Riley, Bp, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, Ab, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, Sarah, Verhage, M, Walters, Jt, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson, Df, Gejman, Pv, Laurent, C, Mowry, Bj, O'Donovan, Mc, Pulver, Ae, Schwab, Sg, Wildenauer, Db, Dudbridge, F, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, Fb, Liang, Ky, Maier, W, Mallet, J, Nertney, Da, Nestadt, G, Norton, N, Papadimitriou, Gn, Ribble, R, Sanders, Ar, Silverman, Jm, Walsh, D, Williams, Nm, Wormley, B, Psychosis Endophenotypes International Consortium, Arranz, Mj, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, Rs, Kalaydjieva, L, Lawrie, S, Lewis, Cm, Linszen, Dh, Mata, I, Mcintosh, A, Murray, Rm, Ophoff, Ra, Van, Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Wellcome Trust Case Control Consortium 2, Donnelly, P, Barroso, I, Blackwell, Jm, Brown, Ma, Casas, Jp, Corvin, Ap, Deloukas, P, Duncanson, A, Jankowski, J, Markus, Hs, Mathew, Cg, Palmer, Cn, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, Rd, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Tashakkori Ghanbaria, A, Waller, Mj, Weston, P, Widaa, S, Whittaker, P, Mccarthy, Mi, Stefansson, K, Scolnick, E, Purcell, S, Mccarroll, Sa, Sklar, P, Hultman, Cm, Sullivan, P. F., Functional Genomics, Molecular and Cellular Neurobiology, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Adult Psychiatry, Ripke, Stephan, O'Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L, Lee, Sang Hong, Sullivan, Patrick F, Multicenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA deCODE Genet, Reykjavik, Iceland Aarhus Univ Hosp, Risskov, Denmark Aarhus Univ, Ctr Integrat Sequencing iSEQ, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Copenhagen, Denmark Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland Cardiff Univ, Sch Med, Ctr Psychiat Genet & Genom, MRC, Cardiff CF10 3AX, S Glam, Wales Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands Univ Clin Psychiat, Dept Child & Adolescent Psychiat, Skopje, Macedonia Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia Statens Serum Inst, DK-2300 Copenhagen, Denmark Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA Kings Coll London, Inst Psychiat, London, England Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, DenmarkQueens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Belgrade, Fac Med, Belgrade, Serbia Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands Kings Coll London, Dept Neurosci, London, England Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA Univ Halle, Dept Psychiat, Halle, Germany Univ Munich, Dept Psychiat, D-80539 Munich, Germany Univ Iceland, Dept Psychiat, Reykjavik, Iceland Landspitali University Hospital Reykjavik, Iceland Tbilisi State Univ, Dept Psychiat, GE-380086 Tbilisi, Rep of Georgia Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands Vrije Univ Amsterdam, Dept Mol & Cellular Neurosci, Amsterdam, Netherlands Natl Inst Hlth & Welf, Mental Hlth & Subst Abuse Serv, Helsinki, Finland Univ Verona, Sect Psychiat, I-37100 Verona, Italy UCL, Inst Cognit Neurosci, London, England UCL, Mental Hlth Sci Unit, London, England Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA Harvard Univ, Sch Med, Dept Genet, Boston, MA USA, Child and Adolescent Psychiatry / Psychology, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Human genetics, NCA - Brain mechanisms in health and disease, and NCA - Neurobiology of mental health

Subjects
Male, Candidate gene, SNP, Single-nucleotide polymorphism, Genome-wide association study, Disease, Biology, heritability, neuronal calcium signaling, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Genetics, medicine, Humans, GWAS, Genetic Predisposition to Disease, Bipolar disorder, 030304 developmental biology, Genetic association, Sweden, Genetics & Heredity, 0303 health sciences, medicine.disease, 3. Good health, genome sequencing, schizophrenia, Schizophrenia, Meta-analysis, Case-Control Studies, genetic variation, Female, genome-wide scan, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder. NIMH R01 MH077139 R01 MH095034 Stanley Center for Psychiatric Research Sylvan Herman Foundation Friedman Brain Institute at the Mount Sinai School of Medicine Karolinska Institutet, Karolinska University Hospital Swedish Research Council Swedish County Council Soderstrom Konigska Foundation Netherlands Scientific Organization NWO 645-000-003 info:eu-repo/grantAgreement/EC/FP7/223423 Danish Strategic Research Council H. Lundbeck A/S Faculty of Health Sciences at Aarhus University Lundbeck Foundation Stanley Research Foundation Wellcome Trust 085475/B/08/Z 085475/Z/08/Z

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results