Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
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Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
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Recent genetic studies indicate a complex polygenic architecture involving hundreds of genetic variants that individually confer a minimal increase on the overall risk of developing schizophrenia.
“recent genetic studies have indicated a complex polygenic architecture involving hundreds of genetic variants that individually confer a minimal increase on the overall risk of developing the disorder (Purcell et al., 2009)”
From DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia (2021) · cites this paper as Purcell et al., 2009
Schizophrenia has an estimated heritability of 60-80%, and a large portion of that heritability is due to common risk alleles.
“Schizophrenia has a heritability of 60–80%, much of which is attributable to common risk alleles.”
From Mapping genomic loci implicates genes and synaptic biology in schizophrenia (2022) · cites this paper as [5]
A large share of between-person variation in schizophrenia risk is genetic and involves many common alleles, rare copy number variants, and rare coding variants.
“Much of the between-individual variation in risk is genetic, involving large numbers of common alleles,5 rare copy number variants (CNVs)6, and rare coding variants (RCVs)7,8.”
From Mapping genomic loci implicates genes and synaptic biology in schizophrenia (2022) · cites this paper as [5]
Quality control parameters were adjusted until lambda GC was between 1.0 and 1.4 before inclusion of principal components and between 1.0 and 1.15 after inclusion of PCA covariates.
“we evaluated the effectiveness of the primary technical and genomic quality control parameters on the genome-wide inflation of test statistics using the lambda GC (median)5 and as necessary made the QC parameters more stringent until this value was between 1.0 and 1.4 (before inclusion of principal components as covariates) and/or between 1.0 and 1.15 after inclusion of PCA covariates.”
From Mapping genomic loci implicates genes and synaptic biology in schizophrenia (2022) · cites this paper as [5]
Development of robust polygenic scores for several common diseases has been catalysed by more precise per-variant effect estimates from larger GWAS, improved algorithms, and large-scale biobanks.
“The development of robust polygenic scores for several common diseases has been catalysed by more precise per-variant effect estimates from larger GWAS datasets, improved algorithms for combining information across millions of single-nucleotide polymorphisms, and large-scale biobanks that support score validation69,146,147.”
From A brief history of human disease genetics (2020) · cites this paper as [146]
Additive effects of genetic risk markers have been documented in schizophrenia and ADHD.
“Additive effects of genetic risk markers were documented in schizophrenia (Purcell et al., 2009) and in ADHD (Jain et al., 2011).”
From From early markers to neuro-developmental mechanisms of autism (2014) · cites this paper as Purcell et al., 2009
Phenotypic expression of rare high-penetrance alleles is modulated by other genetic factors, including rare variants, common polygenic variation, or epigenetic regulation.
“Undoubtedly, the phenotypic expression of rare high-penetrance alleles is modulated by other genetic factors, including rare variants, as well as common (polygenic) variation (Purcell et al., 2009) or epigenetic regulation (Hirasawa and Feil, 2010).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Purcell et al., 2009
The variance explained by the allele score is only about a third of that recently explained for schizophrenia.
“and only about a third of that recently explained for schizophrenia (30)”
From Individual common variants exert weak effects on the risk for autism spectrum disorders (2012) · cites this paper as [30]
Schizophrenia risk is highly polygenic, arising from many genetic variants each with small effects.
“SCZ is truly complex and appears to result from a myriad of genetic variants exerting small effects on disease risk4,5, conforming closely to a classical polygenic model.”
From Gene expression elucidates functional impact of polygenic risk for schizophrenia (2016) · cites this paper as [4]
Schizophrenia results from many genetic variants with small effects, fitting a polygenic model.
“SCZ is truly complex and appears to result from a myriad of genetic variants exerting small effects on disease risk4,5, conforming closely to a classical polygenic model.”
From Gene expression elucidates functional impact of polygenic risk for schizophrenia (2016) · cites this paper as [4]
In humans, using all nominally significant SNPs rather than only GWAS-significant ones captures much more genetic variance than the highly significant loci explain.
“Similarly in humans, by taking all nominally significant SNPs rather than just the GWAS significant ones, it is possible to capture much more of the genetic variance than is explained by the highly significant loci73,74”
From Rare and common variants: twenty arguments (2012) · cites this paper as [73]
The large-scale impact of large numbers of common variants may be a general feature of human complex traits.
“Indeed, the large-scale impact of large numbers of common variants may be a general feature of human complex traits 70–77”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [70]
Hypothesized genetic architectures consisting entirely of rare variants are inconsistent with the data for AD, ASD, BIP, and SCZ (as well as for multiple other complex biomedical diseases).
“Hypothesized genetic architectures consisting entirely of rare variants are inconsistent with the data for AD, ASD, BIP, and SCZ (as well as for multiple other complex biomedical diseases). 70–77”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [70]
Common variant SNP effects have been estimated to explain large proportions of the phenotypic heritability for a wide range of diseases: BIP and SCZ; T1DM, T2DM, Crohn's disease, rheumatoid arthritis, celiac disease, and coronary artery disease; and continuous traits (height, intelligence, and body mass).
“Common variant SNP effects have been estimated to explain large proportions of the phenotypic heritability for a wide range of diseases: BIP and SCZ; 69,130 T1DM, T2DM, Crohn’s disease, rheumatoid arthritis, celiac disease, and coronary artery disease; 70,77 and continuous traits (height, intelligence, and body mass). 70,131,132”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [70]
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Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
XV.—The Correlation between Relatives on the Supposition of Mendelian Inheritance.
Fisher, R. A. (1919) · Transactions of the Royal Society of Edinburgh · doi:10.1017/s0080456800012163 · Cited by 4,387 · see citing works
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714 · see citing works
Schizophrenia as a Complex Trait: Evidence From a Meta-analysis of Twin Studies
Sullivan, P. F., Kendler, K. S., & Neale, M. C. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.12.1187 · Cited by 2,356 · see citing works
Lichtenstein, P., Yip, B. H., Björk, C., Pawitan, Y., Cannon, T. D., Sullivan, P. F., & Hultman, C. M. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60072-6 · Cited by 2,125 · see citing works
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800 · see citing works
Personal genomes: The case of the missing heritability
Maher, B. (2008) · Nature · doi:10.1038/456018a · Cited by 1,737 · see citing works
Common variants conferring risk of schizophrenia
†Genetic Risk and Outcome in Psychosis (GROUP), Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Cichon, S., Rujescu, D., Werge, T., Pietiläinen, O. P. H., Mors, O., et al. (2009) · Nature · doi:10.1038/nature08186 · Cited by 1,677 · see citing works
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475 · see citing works
Common variants on chromosome 6p22.1 are associated with schizophrenia
Shi, J., Levinson, D. F., Duan, J., Sanders, A. R., Zheng, Y., Pe’er, I., Dudbridge, F., Holmans, P., Whittemore, A. S., Mowry, B. J., et al. (2009) · Nature · doi:10.1038/nature08192 · Cited by 1,154 · see citing works
Identification of loci associated with schizophrenia by genome-wide association and follow-up
Molecular Genetics of Schizophrenia Collaboration, O'Donovan, M. C., Craddock, N., Norton, N., Williams, H., Peirce, T., Moskvina, V., Nikolov, I., Hamshere, M., Carroll, L., et al. (2008) · Nature Genetics · doi:10.1038/ng.201 · Cited by 1,070 · see citing works
A HapMap harvest of insights into the genetics of common disease
Manolio, T. A., Brooks, L. D., & Collins, F. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34772 · Cited by 889 · see citing works
Genome-wide association analysis identifies 20 loci that influence adult height
Initiative, D. G., Weedon, M. N., The Wellcome Trust Case Control Consortium, Cambridge GEM Consortium, Lango, H., Lindgren, C. M., Wallace, C., Evans, D. M., Mangino, M., Freathy, R. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.121 · Cited by 826 · see citing works
Strong association of de novo copy number mutations with sporadic schizophrenia
Xu, B., Roos, J. L., Levy, S., van Rensburg, E. J., Gogos, J. A., & Karayiorgou, M. (2008) · Nature Genetics · doi:10.1038/ng.162 · Cited by 813 · see citing works
Korn, J. M., Kuruvilla, F. G., McCarroll, S. A., Wysoker, A., Nemesh, J., Cawley, S., Hubbell, E., Veitch, J., Collins, P. J., Darvishi, K., et al. (2008) · Nature Genetics · doi:10.1038/ng.237 · Cited by 783 · see citing works
Prediction of individual genetic risk to disease from genome-wide association studiesPreprint
Wray, N. R., Goddard, M. E., & Visscher, P. M. (2007) · Genome Research · doi:10.1101/gr.6665407 · Cited by 714 · see citing works
Whole-genome association study of bipolar disorder
Sklar, P. B., Smoller, J. W., Fan, J., Ferreira, M. A. R., Perlis, R. H., Chambert, K., Nimgaonkar, V. L., McQueen, M. B., Faraone, S. V., Kirby, A. W., et al. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002151 · Cited by 691 · see citing works
A polygenic theory of schizophrenia.
Gottesman, I. I., & Shields, J. (1967) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.58.1.199 · Cited by 636 · see citing works
Genes for Schizophrenia and Bipolar Disorder? Implications for Psychiatric Nosology
Craddock, N. (2005) · Schizophrenia Bulletin · doi:10.1093/schbul/sbj033 · Cited by 496 · see citing works
Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders
Psychiatric GWAS Consortium Coordinating Committee (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08091354 · Cited by 450 · see citing works
Variation analysis and gene annotation of eight MHC haplotypes: The MHC Haplotype Project
Horton, R., Gibson, R., Coggill, P. C., Miretti, M. M., Allcock, R. J. N., Almeida, J. P., Forbes, S. A., Gilbert, J. G. R., Halls, K., Harrow, J., et al. (2008) · Immunogenetics · doi:10.1007/s00251-007-0262-2 · Cited by 317 · see citing works
Schizophrenia: a common disease caused by multiple rare alleles
McClellan, J. M., Susser, E., & King, M.-C. (2007) · British Journal of Psychiatry · doi:10.1192/bjp.bp.106.025585 · Cited by 296 · see citing works
A framework for interpreting genome-wide association studies of psychiatric disorders
The Psychiatric GWAS Consortium Steering Committee (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.126 · Cited by 208 · see citing works
The NOTCH4 locus is associated with susceptibility to schizophrenia
Wei, J., & Hemmings, G. P. (2000) · Nature Genetics · doi:10.1038/78044 · Cited by 180 · see citing works
Phenotypic and genetic complexity of psychosis
Craddock, N. J., O’Donovan, M. C., & Owen, M. J. (2007) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.106.033761 · Cited by 103 · see citing works
Invited commentary on Mental health of looked after children
Vostanis, P. (2003) · Advances in Psychiatric Treatment · doi:10.1192/apt.9.4.256 · Cited by 83 · see citing works
Dissecting the phenotype in genome-wide association studies of psychiatric illness
Craddock, N. J., Kendler, K. S., Neale, M. C., Nürnberger, J. I., Purcell, S., Rietschel, M., Perlis, R. H., Santangelo, S. L., Schulze, T. G., Schulze, T. G., et al. (2009) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.108.063156 · Cited by 72 · see citing works
Fertility of first-degree relatives of patients with schizophrenia: A three generation perspective
Svensson, A. C., Lichtenstein, P., Sandin, S., & Hultman, C. M. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2006.12.002 · Cited by 53 · see citing works
Cardno, A. G., & Gottesman, I. I. (2000) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(200021)97:1
Flagged first, then by citations
1 of the 31 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
GCTA: a tool for genome-wide complex trait analysis
Yang, J., Lee, S. H., Goddard, M. E., & Visscher, P. M. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.11.011 · Cited by 8,279 · see citing works
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577 · see citing works
Mendelian randomization: genetic anchors for causal inference in epidemiological studies
Davey Smith, G., & Hemani, G. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu328 · Cited by 4,677 · see citing works
Common SNPs explain a large proportion of the heritability for human height
Yang, J., Benyamin, B., McEvoy, B. P., Gordon, S., Henders, A. K., Nyholt, D. R., Madden, P. A., Heath, A. C., Martin, N. G., Montgomery, G. W., et al. (2010) · Nature Genetics · doi:10.1038/ng.608 · Cited by 4,446 · see citing works
An atlas of genetic correlations across human diseases and traits
ReproGen Consortium, Bulik-Sullivan, B., Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P.-R., Duncan, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3406 · Cited by 4,255 · see citing works
10 Years of GWAS Discovery: Biology, Function, and Translation
Visscher, P. M., Wray, N. R., Zhang, Q., Sklar, P., McCarthy, M. I., Brown, M. A., & Yang, J. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.06.005 · Cited by 3,719 · see citing works
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA
Maurano, M. T., Humbert, R., Rynes, E., Thurman, R. E., Haugen, E., Wang, H., Reynolds, A. P., Sandstrom, R., Qu, H., Brody, J., et al. (2012) · Science · doi:10.1126/science.1222794 · Cited by 3,716 · see citing works
(2013) · The Lancet · doi:10.1016/s0140-6736(12)62129-1 · Cited by 3,010 · see citing works
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Trubetskoy, V., Pardiñas, A. F., Qi, T., Panagiotaropoulou, G., Awasthi, S., Bigdeli, T. B., Bryois, J., Chen, C.-Y., Dennison, C. A., Hall, L. S., et al. (2022) · Nature · doi:10.1038/s41586-022-04434-5 · Cited by 2,964 · see citing works
Khera, A. V., Chaffin, M., Aragam, K. G., Haas, M. E., Roselli, C., Choi, S. H., Natarajan, P., Lander, E. S., Lubitz, S. A., Ellinor, P. T., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0183-z · Cited by 2,953 · see citing works
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
MAGIC, Speliotes, E. K., on behalf of Procardis Consortium, Willer, C. J., Berndt, S. I., Monda, K. L., Thorleifsson, G., Jackson, A. U., Allen, H. L., Lindgren, C. M., et al. (2010) · Nature Genetics · doi:10.1038/ng.686 · Cited by 2,912 · see citing works
An Expanded View of Complex Traits: From Polygenic to Omnigenic
Boyle, E. A., Li, Y. I., & Pritchard, J. K. (2017) · Cell · doi:10.1016/j.cell.2017.05.038 · Cited by 2,851 · see citing works
Howard, D. M., Adams, M. J., Clarke, T.-K., Hafferty, J. D., Gibson, J., Shirali, M., Coleman, J. R. I., Hagenaars, S. P., Ward, J., Wigmore, E. M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0326-7 · Cited by 2,565 · see citing works
Integrative approaches for large-scale transcriptome-wide association studies
Gusev, A., Ko, A., Shi, H., Bhatia, G., Chung, W., Penninx, B. W. J. H., Jansen, R., de Geus, E. J. C., Boomsma, D. I., Wright, F. A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3506 · Cited by 2,479 · see citing works
Schizophrenia risk from complex variation of complement component 4
Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., Tooley, K., Presumey, J., Baum, M., Van Doren, V., et al. (2016) · Nature · doi:10.1038/nature16549 · Cited by 2,394 · see citing works
Visscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.029 · Cited by 2,425 · see citing works
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) · Nature Genetics · doi:10.1038/ng.2711 · Cited by 2,263 · see citing works
ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Demontis, D., Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Walters, R. K., Martin, J., Mattheisen, M., Als, T. D., Agerbo, E., Baldursson, G., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0269-7 · Cited by 2,203 · see citing works
Animal models of neuropsychiatric disorders
Nestler, E. J., & Hyman, S. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2647 · Cited by 2,023 · see citing works
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Lango Allen, H., Estrada, K., Lettre, G., Berndt, S. I., Weedon, M. N., Rivadeneira, F., Willer, C. J., Jackson, A. U., Vedantam, S., Raychaudhuri, S., et al. (2010) · Nature · doi:10.1038/nature09410 · Cited by 1,945 · see citing works
Analysis of shared heritability in common disorders of the brain
The Brainstorm Consortium, Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., Escott-Price, V., Falcone, G. J., Gormley, P., et al. (2018) · Science · doi:10.1126/science.aap8757 · Cited by 1,924 · see citing works
Polygenic prediction via Bayesian regression and continuous shrinkage priors
Ge, T., Chen, C.-Y., Ni, Y., Feng, Y.-C. A., & Smoller, J. W. (2019) · Nature Communications · doi:10.1038/s41467-019-09718-5 · Cited by 1,922 · see citing works
Genome-wide association study identifies five new schizophrenia loci
The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) · Nature Genetics · doi:10.1038/ng.940 · Cited by 1,919 · see citing works
Tutorial: a guide to performing polygenic risk score analyses
Choi, S. W., Mak, T. S. H., & O’Reilly, P. F. (2020) · Nature Protocols · doi:10.1038/s41596-020-0353-1 · Cited by 1,913 · see citing works
Genome-wide association studies
Uffelmann, E., Huang, Q. Q., Munung, N. S., de Vries, J., Okada, Y., Martin, A. R., Martin, H. C., Lappalainen, T., & Posthuma, D. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00056-9 · Cited by 1,849 · see citing works
Insel, T. R. (2010) · Nature · doi:10.1038/nature09552 · Cited by 1,783 · see citing works
Goldsmith, D. R., Rapaport, M. H., & Miller, B. J. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.3 · Cited by 1,683 · see citing works
Common variants conferring risk of schizophrenia
†Genetic Risk and Outcome in Psychosis (GROUP), Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Cichon, S., Rujescu, D., Werge, T., Pietiläinen, O. P. H., Mors, O., et al. (2009) · Nature · doi:10.1038/nature08186 · Cited by 1,677 · see citing works
Missing heritability and strategies for finding the underlying causes of complex disease
Eichler, E. E., Jonathan Flint, C., Gibson, G. C., Kong, A., Leal, S. M., Moore, J. H., & Nadeau, J. H. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2809 · Cited by 1,671 · see citing works
Biological studies of post-traumatic stress disorder
Pitman, R. K., Rasmusson, A. M., Koenen, K. C., Shin, L. M., Orr, S. P., Gilbertson, M. W., Milad, M. R., & Liberzon, I. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3339 · Cited by 1,529 · see citing works
Genomewide Association Studies and Assessment of the Risk of Disease
Manolio, T. A. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0905980 · Cited by 1,512 · see citing works
Power and predictive accuracy of polygenic risk scores
Dudbridge, F. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003348 · Cited by 1,509 · see citing works
“Schiz [3] MS [6] BrCa [14] PrCa [14] RA [9] Celiac [9] MI/CAD [9] T2D [9]”
BackgroundMethodResultInfluentialGenome-wide association analysis identifies 13 new risk loci for schizophrenia
Multicenter Genetic Studies of Schizophrenia Consortium, Ripke, S., Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2742 · Cited by 1,496 · see citing works
Evaluating the potential role of pleiotropy in Mendelian randomization studies
Hemani, G., Bowden, J., & Davey Smith, G. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy163 · Cited by 1,496 · see citing works
Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations
Martin, A. R., Gignoux, C. R., Walters, R. K., Wojcik, G. L., Neale, B. M., Gravel, S., Daly, M. J., Bustamante, C. D., & Kenny, E. E. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.03.004 · Cited by 1,391 · see citing works
A polygenic burden of rare disruptive mutations in schizophrenia
Purcell, S. M., Moran, J. L., Fromer, M., Ruderfer, D., Solovieff, N., Roussos, P., O’Dushlaine, C., Chambert, K., Bergen, S. E., Kähler, A., et al. (2014) · Nature · doi:10.1038/nature12975 · Cited by 1,385 · see citing works
Psychiatric GWAS Consortium Bipolar Disorder Working Group, Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., Edenberg, H. J., Nurnberger, J. I., Rietschel, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.943 · Cited by 1,344 · see citing works
Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores
Vilhjálmsson, B. J., Yang, J., Finucane, H. K., Gusev, A., Lindström, S., Ripke, S., Genovese, G., Loh, P.-R., Bhatia, G., Do, R., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.09.001 · Cited by 1,303 · see citing works
Genome-wide association study identifies 74 loci associated with educational attainment
Okbay, A., Beauchamp, J. P., Fontana, M. A., Lee, J. J., Pers, T. H., Rietveld, C. A., Turley, P., Chen, G.-B., Emilsson, V., Meddens, S. F. W., et al. (2016) · Nature · doi:10.1038/nature17671 · Cited by 1,297 · see citing works
Rare and common variants: twenty arguments
Gibson, G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3118 · Cited by 1,278 · see citing works
Prenatal Infection and Schizophrenia: A Review of Epidemiologic and Translational Studies
Brown, A. S., & Derkits, E. J. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09030361 · Cited by 1,269 · see citing works
Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5)
Ma, F. (2020) · Springer eBooks · doi:10.1007/978-3-319-69892-2_419-2 · Cited by 1,241 · see citing works
Most genetic risk for autism resides with common variation
Gaugler, T., Klei, L., Sanders, S. J., Bodea, C. A., Goldberg, A. P., Lee, A. B., Mahajan, M., Manaa, D., Pawitan, Y., Reichert, J., et al. (2014) · Nature Genetics · doi:10.1038/ng.3039 · Cited by 1,239 · see citing works
Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
Seshadri, S. (2010) · JAMA · doi:10.1001/jama.2010.574 · Cited by 1,219 · see citing works
Genetic architectures of psychiatric disorders: the emerging picture and its implications
Sullivan, P. F., Daly, M. J., & O'Donovan, M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3240 · Cited by 1,177 · see citing works
Common variants on chromosome 6p22.1 are associated with schizophrenia
Shi, J., Levinson, D. F., Duan, J., Sanders, A. R., Zheng, Y., Pe’er, I., Dudbridge, F., Holmans, P., Whittemore, A. S., Mowry, B. J., et al. (2009) · Nature · doi:10.1038/nature08192 · Cited by 1,154 · see citing works
PRSice: Polygenic Risk Score software
Euesden, J., Lewis, C. M., & O’Reilly, P. F. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu848 · Cited by 1,149 · see citing works
Kahn, R. S., Sommer, I. E., Murray, R. M., Meyer‐Lindenberg, A., Weinberger, D. R., Cannon, T. D., O’Donovan, M. C., Correll, C. U., Kane, J. M., van Os, J., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.67 · Cited by 1,132 · see citing works
Epigenetic transmission of the impact of early stress across generations
Franklin, T. B., Russig, H., Weiss, I. C., Gräff, J., Linder, N., Michalon, A., Vizi, S., & Mansuy, I. M. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.036 · Cited by 1,125 · see citing works
A mega-analysis of genome-wide association studies for major depressive disorder
Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Ripke, S., Wray, N. R., Lewis, C. M., Hamilton, S. P., Weissman, M. M., Breen, G., Byrne, E. M., Blackwood, D. H. R., Boomsma, D. I., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.21 · Cited by 1,120 · see citing works
Gene expression elucidates functional impact of polygenic risk for schizophrenia
Fromer, M., Roussos, P., Sieberts, S. K., Johnson, J. S., Kavanagh, D. H., Perumal, T. M., Ruderfer, D. M., Oh, E. C., Topol, A., Shah, H. R., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4399 · Cited by 1,091 · see citing works
Pleiotropy in complex traits: challenges and strategies
Solovieff, N., Cotsapas, C., Lee, P. H., Purcell, S. M., & Smoller, J. W. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3461 · Cited by 1,085 · see citing works
Large-scale genotyping identifies 41 new loci associated with breast cancer risk
Michailidou, K., kConFab Investigators, Australian Ovarian Cancer Study Group, The GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, Hall, P. N., González‐Neira, A., Ghoussaini, M., Dennis, J., Milne, R. L., Schmidt, M. K., et al. (2013) · Nature Genetics · doi:10.1038/ng.2563 · Cited by 1,066 · see citing works
The Diagnosis of Mental Disorders: The Problem of Reification
Hyman, S. E. (2010) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.3.022806.091532 · Cited by 1,052 · see citing works
Initial impact of the sequencing of the human genome
Lander, E. S. (2011) · Nature · doi:10.1038/nature09792 · Cited by 1,044 · see citing works
Analysis of polygenic risk score usage and performance in diverse human populations
Duncan, L., Shen, H., Gelaye, B., Meijsen, J., Ressler, K., Feldman, M., Peterson, R., & Domingue, B. (2019) · Nature Communications · doi:10.1038/s41467-019-11112-0 · Cited by 1,038 · see citing works
“2 (see schizophrenia and Purcell 2009 in the citation information for this point).”
BackgroundStudy, L. C., Okbay, A., Baselmans, B. M. L., De Neve, J.-E., Turley, P., Nivard, M. G., Fontana, M. A., Meddens, S. F. W., Linnér, R. K., Rietveld, C. A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3552 · Cited by 1,013 · see citing works
Comprehensive functional genomic resource and integrative model for the human brain
Wang, D., Liu, S., Warrell, J., Won, H., Shi, X., Navarro, F. C. P., Clarke, D., Gu, M., Emani, P., Yang, Y. T., et al. (2018) · Science · doi:10.1126/science.aat8464 · Cited by 965 · see citing works
Structure and function of complex brain networks
Sporns, O. (2013) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2013.15.3/osporns · Cited by 931 · see citing works
Genome partitioning of genetic variation for complex traits using common SNPs
Yang, J., Manolio, T. A., Pasquale, L. R., Boerwinkle, E., Caporaso, N., Cunningham, J. M., de Andrade, M., Feenstra, B., Feingold, E., Hayes, M. G., et al. (2011) · Nature Genetics · doi:10.1038/ng.823 · Cited by 890 · see citing works
Xue, A., Wu, Y., Zhu, Z., Zhang, F., Kemper, K. E., Zheng, Z., Yengo, L., Lloyd‐Jones, L. R., Sidorenko, J., Wu, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04951-w · Cited by 884 · see citing works
Zheng, J., Erzurumluoglu, A. M., Elsworth, B. L., Kemp, J. P., Howe, L., Haycock, P. C., Hemani, G., Tansey, K., Laurin, C., Early Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium, et al. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btw613 · Cited by 869 · see citing works
Rare Variants Create Synthetic Genome-Wide Associations
Dickson, S. P., Wang, K., Krantz, I., Hakonarson, H., & Goldstein, D. B. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000294 · Cited by 857 · see citing works
CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics
Malhotra, D., & Sebat, J. (2012) · Cell · doi:10.1016/j.cell.2012.02.039 · Cited by 854 · see citing works
The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
the Alzheimer’s Disease Neuroimaging Initiative, E. C., Thompson, P. M., Stein, J. L., Medland, S. E., Hibar, D. P., Vasquez, A. A., Renteria, M. E., Toro, R., Jahanshad, N., Schumann, G., et al. (2014) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9269-5 · Cited by 838 · see citing works
GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment
Rietveld, C. A., Medland, S. E., Derringer, J., Yang, J., Esko, T., Martin, N. W., Westra, H.-J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., et al. (2013) · Science · doi:10.1126/science.1235488 · Cited by 827 · see citing works
A tutorial on conducting genome‐wide association studies: Quality control and statistical analysis
Marees, A. T., de Kluiver, H., Stringer, S., Vorspan, F., Curis, E., Cynthia Marie-claire, A., & Derks, E. M. (2018) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.1608 · Cited by 820 · see citing works
Peterson, R. E., Kuchenbaecker, K., Walters, R. K., Chen, C.-Y., Popejoy, A. B., Periyasamy, S., Lam, M., Iyegbe, C., Strawbridge, R. J., Brick, L., et al. (2019) · Cell · doi:10.1016/j.cell.2019.08.051 · Cited by 797 · see citing works
Developing constructs for psychopathology research: Research domain criteria
Sanislow, C. A., Pine, D. S., Quinn, K. J., Kozak, M. J., Garvey, M. A., Heinssen, R. K., Wang, P. S.-E., & Cuthbert, B. N. (2010) · Journal of Abnormal Psychology · doi:10.1037/a0020909 · Cited by 793 · see citing works
Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood
Khera, A. V., Chaffin, M., Wade, K. H., Zahid, S., Brancale, J., Xia, R., Distefano, M., Senol-Cosar, O., Haas, M. E., Bick, A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.028 · Cited by 789 · see citing works
Rasic, D., Hajek, T., Alda, M., & Uher, R. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbt114 · Cited by 758 · see citing works
23and Me Research Team, Karlsson Linnér, R., eQTLgen Consortium, International Cannabis Consortium, Social Science Genetic Association Consortium, Biroli, P., Kong, E., Meddens, S. F. W., Wedow, R., Fontana, M. A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0309-3 · Cited by 756 · see citing works
Genetic essentialism: On the deceptive determinism of DNA.
Dar‐Nimrod, I., & Heine, S. J. (2010) · Psychological Bulletin · doi:10.1037/a0021860 · Cited by 744 · see citing works
The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood
Lichtenstein, P., Carlström, E., Råstam, M., Gillberg, C., & Anckarsäter, H. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10020223 · Cited by 738 · see citing works
LDpred2: better, faster, stronger
Privé, F., Arbel, J., & Vilhjálmsson, B. J. (2021) · Bioinformatics · doi:10.1093/bioinformatics/btaa1029 · Cited by 726 · see citing works
Aragam, K. G., Jiang, T., Goel, A., Kanoni, S., Wolford, B. N., Atri, D. S., Weeks, E. M., Wang, M., Hindy, G., Zhou, W., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01233-6 · Cited by 721 · see citing works
Improving polygenic prediction in ancestrally diverse populations
Ruan, Y., Lin, Y.-F., Feng, Y.-C. A., Chen, C.-Y., Lam, M., Guo, Z., Initiatives, S. G. A., Ahn, Y. M., Akiyama, K., Arai, M., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01054-7 · Cited by 707 · see citing works
Developing and evaluating polygenic risk prediction models for stratified disease prevention
Chatterjee, N., Shi, J., & García‐Closas, M. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.27 · Cited by 698 · see citing works
A brief history of human disease genetics
Claussnitzer, M., Cho, J. H., Collins, R., Cox, N. J., Dermitzakis, E. T., Hurles, M. E., Kathiresan, S., Kenny, E. E., Lindgren, C. M., MacArthur, D. G., et al. (2020) · Nature · doi:10.1038/s41586-019-1879-7 · Cited by 697 · see citing works
The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation
Lambert, S. A., Gil, L., Jupp, S., Ritchie, S. C., Xu, Y., Buniello, A., McMahon, A., Abraham, G., Chapman, M., Parkinson, H., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00783-5 · Cited by 690 · see citing works
Psychiatric Genomics: An Update and an Agenda
Sullivan, P. F., Agrawal, A., Bulik, C. M., Andreassen, O. A., Børglum, A. D., Breen, G., Cichon, S., Edenberg, H. J., Faraone, S. V., Gelernter, J., et al. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17030283 · Cited by 676 · see citing works
Pitfalls of predicting complex traits from SNPs
Wray, N. R., Yang, J., Hayes, B. J., Price, A. L., Goddard, M. E., & Visscher, P. M. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3457 · Cited by 672 · see citing works
Common disorders are quantitative traits
Plomin, R., Haworth, C. M. A., & Davis, O. S. P. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2670 · Cited by 670 · see citing works
The environment and susceptibility to schizophrenia
Brown, A. S. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.09.003 · Cited by 664 · see citing works
THE QTN PROGRAM AND THE ALLELES THAT MATTER FOR EVOLUTION: ALL THAT'S GOLD DOES NOT GLITTER
Rockman, M. V. (2011) · Evolution · doi:10.1111/j.1558-5646.2011.01486.x · Cited by 661 · see citing works
Research Review: Polygenic methods and their application to psychiatric traits
Wray, N. R., Lee, S., Mehta, D., Vinkhuyzen, A. A. E., Dudbridge, F., & Middeldorp, C. M. (2014) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12295 · Cited by 657 · see citing works
Comparative genetic architectures of schizophrenia in East Asian and European populations
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lam, M., Indonesia Schizophrenia Consortium, Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN), Chen, C.-Y., Li, Z., Martin, A. R., Bryois, J., Ma, X., Gaspar, H., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0512-x · Cited by 655 · see citing works
Berndt, S. I., Gustafsson, S., Mägi, R., Ganna, A., Wheeler, E., Feitosa, M. F., Justice, A. E., Monda, K. L., Croteau-Chonka, D. C., Day, F. R., et al. (2013) · Nature Genetics · doi:10.1038/ng.2606 · Cited by 646 · see citing works
Craddock, N. J., & Sklar, P. B. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60855-7 · Cited by 635 · see citing works
Day, F., Karaderi, T., Jones, M. R., Meun, C., He, C., Drong, A., Kraft, P., Lin, N., Huang, H., Broer, L., et al. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007813 · Cited by 619 · see citing works
Consanguinity, human evolution, and complex diseases
Bittles, A. H., & Black, M. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906079106 · Cited by 620 · see citing works
What kinds of things are psychiatric disorders?
Kendler, K. S., Zachar, P., & Craver, C. F. (2010) · Psychological Medicine · doi:10.1017/s0033291710001844 · Cited by 612 · see citing works
Genome-wide association studies establish that human intelligence is highly heritable and polygenic
Davies, G., Tenesa, A., Payton, A., Yang, J., Harris, S. E., Liewald, D., Ke, X., Le Hellard, S., Christoforou, A., Luciano, M., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.85 · Cited by 608 · see citing works
Barnes, T. R. E., Drake, R., Paton, C., Cooper, S. J., Deakin, J. F. W., Ferrier, I. N., Gregory, C. J., Haddad, P. M., Howes, O. D., Jones, I. R., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119889296 · Cited by 607 · see citing works
Stroke genetics informs drug discovery and risk prediction across ancestries
Mishra, A., Malik, R., Hachiya, T., Jürgenson, T., Namba, S., Posner, D. C., Kamanu, F., Koido, M., Grand, Q. L., Shi, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05165-3 · Cited by 591 · see citing works
The Kraepelinian dichotomy – going, going … but still not gone
Craddock, N., & Owen, M. J. (2010) · British Journal of Psychiatry · doi:10.1192/bjp.bp.109.073429 · Cited by 587 · see citing works
The Hippocampal Formation in Schizophrenia
Tamminga, C. A., Stan, A. D., & Wagner, A. D. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09081187 · Cited by 583 · see citing works
Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs
The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), Lee, S. H., The International Schizophrenia Consortium (ISC), The Molecular Genetics of Schizophrenia Collaboration (MGS), DeCandia, T. R., Ripke, S., Yang, J., Sullivan, P. F., Goddard, M. E., Keller, M. C., et al. (2012) · Nature Genetics · doi:10.1038/ng.1108 · Cited by 579 · see citing works
Talkowski, M. E., Rosenfeld, J. A., Blumenthal, I., Pillalamarri, V., Chiang, C., Heilbut, A., Ernst, C., Hanscom, C., Rossin, E., Lindgren, A. M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.028 · Cited by 577 · see citing works
Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment
Bisgaard, T. H., Allin, K. H., Keefer, L., Ananthakrishnan, A. N., & Jess, T. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00634-6 · Cited by 572 · see citing works
- Authors
- The International Schizophrenia Consortium
- Venue
- Nature
- Published
- 2009-07-01
- Volume
- 460
- Issue
- 7256
- Pages
- 748-752
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3912837
- OpenAlex
- W2098597355
- Cited by
- 4,821
- References
- 31
- Citations by year
- 2026: 84 · 2025: 129 · 2024: 190 · 2023: 235 · 2022: 246 · 2021: 291 · 2020: 354 · 2019: 337 · 2018: 297 · 2017: 339 · 2016: 365 · 2015: 328 · 2014: 316 · 2013: 330 · 2012: 348
- FWCI
- 197.43
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Funders
- Massachusetts Institute of Technology
- Wellcome Trust (066717)
- Broad Institute
- National Institute of Mental Health (R01MH077139, P50MH066392, R01MH071681, R01MH062137, R01MH074027, R01MH080403)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- schizophrenia, bipolar disorder, polygenic risk, common genetic variants, major histocompatibility complex, genetic susceptibility, immunity, heritability, psychiatric genetics
- MeSH terms
- Alleles, Bipolar Disorder, Europe, Female, Gene Frequency, Humans, Major Histocompatibility Complex, Male, Models, Genetic, Schizophrenia, Genetic Variation, Genome, Human, Case-Control Studies, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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