Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia
Abstract
We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ∼50% that achieved nominal significance and ∼75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.
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Even when non-European cohorts are only a fraction the size of the largest European study, they are likely to have disproportionate value for predicting polygenic traits in other individuals of similar ancestry.
“These studies have shown that even when non-European cohorts are only a fraction the size of the largest European study, they are likely to have disproportionate value for predicting polygenic traits in other individuals of similar ancestry.”
From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [24]
The polygenic risk score results (pp. 17–18) show that adding the smaller Chinese cohort improved prediction of schizophrenia case-control status in a Chinese target sample; at one threshold, variance explained rose from 2.34% with European-only training to 7.86% with combined training. The sample-size comparison (p. 9) supports the cohort-size premise. The paper studies schizophrenia in Chinese ancestry, however, not polygenic traits generally or non-European cohorts generally. (LLM, conf=0.88)
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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
An integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711 · 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
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368 · see citing works
Self-citationLD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bulik-Sullivan, B. K., Loh, P.-R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., Daly, M. J., Price, A. L., & Neale, B. M. (2015) · Nature Genetics · doi:10.1038/ng.3211 · Cited by 5,559 · see citing works
Self-citationCommon polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821 · see citing works
Howie, B. N., Donnelly, P., & Marchini, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000529 · Cited by 3,928 · 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
Genome-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
Self-citationBiological interpretation of genome-wide association studies using predicted gene functions
Pers, T. H., Karjalainen, J. M., Chan, Y., Westra, H.-J., Wood, A. R., Yang, J., Lui, J. C., Vedantam, S., Gustafsson, S., Esko, T., et al. (2015) · Nature Communications · doi:10.1038/ncomms6890 · Cited by 787 · see citing works
Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain
Gibbs, J. R., van der Brug, M. P., Hernandez, D. G., Traynor, B. J., Nalls, M. A., Lai, S.-L., Arepalli, S., Dillman, A., Rafferty, I. P., Troncoso, J., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000952 · Cited by 769 · see citing works
Han, B., & Eskin, E. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.04.014 · Cited by 680 · see citing works
Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases
Gusev, A., Lee, S. H., Trynka, G., Finucane, H., Vilhjálmsson, B. J., Xu, H., Zang, C., Ripke, S., Bulik-Sullivan, B., Stahl, E., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.10.004 · Cited by 544 · see citing works
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Flagged first, then by citations
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Sorted by citations
Clinical use of current polygenic risk scores may exacerbate health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2019) · Nature Genetics · doi:10.1038/s41588-019-0379-x · Cited by 2,831 · see citing works
Current clinical use of polygenic scores will risk exacerbating health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2018) · doi:10.1101/441261 · Cited by 2,813 · see citing works
Benefits and limitations of genome-wide association studies
Tam, V., Patel, N. K., Turcotte, M., Bossé, Y., Paré, G., & Meyre, D. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0127-1 · Cited by 2,092 · see citing works
Grotzinger, A. D., Rhemtulla, M., de Vlaming, R., Ritchie, S. J., Mallard, T. T., Hill, W. D., Ip, H. F., Marioni, R. E., McIntosh, A. M., Deary, I. J., et al. (2019) · Nature Human Behaviour · doi:10.1038/s41562-019-0566-x · Cited by 958 · see citing works
Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Michelle Luciano, A., Hill, W. D., Hagenaars, S. P., Ritchie, S. J., Marioni, R. E., Fawns‐Ritchie, C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04362-x · Cited by 668 · 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
“Compared with the latest study using only Chinese individuals 8 , our study has about twice the sample size, and is much more diverse.”
InfluentialSelf-citationGenetic architecture: the shape of the genetic contribution to human traits and disease
Timpson, N. J., Greenwood, C. M. T., Soranzo, N., Lawson, D. J., & Richards, J. B. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.101 · Cited by 434 · see citing works
“37 Even the same trait measured at different anatomical sites can have a divergent genetic architecture.”
BackgroundAdvancing human genetics research and drug discovery through exome sequencing of the UK Biobank
Szustakowski, J. D., Balasubramanian, S., Kvikstad, E., Khalid, S., Bronson, P. G., Sasson, A., Wong, E., Liu, D., Wade Davis, J., Haefliger, C., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00885-0 · Cited by 401 · see citing works
Self-citationCorces, M. R., Shcherbina, A., Kundu, S., Gloudemans, M. J., Frésard, L., Granja, J. M., Louie, B. H., Eulalio, T., Shams, S., Bagdatli, S. T., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-00721-x · Cited by 358 · see citing works
Self-citationZhao, B., Luo, T., Li, T., Li, Y., Zhang, J., Shan, Y., Wang, X., Yang, L., Zhou, F., Zhu, Z., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0516-6 · Cited by 295 · see citing works
EEG microstates are a candidate endophenotype for schizophrenia
da Cruz, J. N., Favrod, O., Roinishvili, M., Chkonia, E. D., Brand, A., Möhr, C., Figueiredo, P., & Herzog, M. H. (2020) · Nature Communications · doi:10.1038/s41467-020-16914-1 · Cited by 255 · see citing works
Meier, S. M., Trontti, K., Purves, K. L., Als, T. D., Grove, J., Laine, M., Pedersen, M. G., Bybjerg-Grauholm, J., Bækved-Hansen, M., Sokolowska, E., et al. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.1119 · Cited by 240 · see citing works
The synaptic hypothesis of schizophrenia version III: a master mechanism
Howes, O. D., & Onwordi, E. C. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02043-w · Cited by 236 · see citing works
“These include VRK2, encoding vaccinia-associated kinase 2, which is involved in neurodevelopmental microglia-mediated synaptic elimination [56], CUL3, encoding Culin-3, which is involved in neural development, glutamate receptor turnover and maintenance of excitation-inhibition balance [56, 67, 68], KALRN, encoding ka…”
BackgroundAdvancing Human Genetics Research and Drug Discovery through Exome Sequencing of the UK BiobankPreprint
Szustakowski, J. D., Balasubramanian, S., Sasson, A., Khalid, S., Bronson, P., Kvikstad, E., Wong, E., Liu, D., Davis, J., Haefliger, C., et al. (2020) · medRxiv · doi:10.1101/2020.11.02.20222232 · Cited by 222 · see citing works
Coleman, J. R. I., Gaspar, H. A., Bryois, J., Byrne, E. M., Forstner, A. J., Holmans, P. A., de Leeuw, C. A., Mattheisen, M., McQuillin, A., Whitehead Pavlides, J. M., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.10.015 · Cited by 199 · see citing works
“MOOD loci overlapped considerably with those found in previous studies of depression and depressive symptoms (51 of 73 loci) (20,23,48–52), bipolar disorder (3 of 73 loci) (53–56), neuroticism (32 of 73 loci) (23,57–59), and schizophrenia (15 of 73 loci) (32,60), although there is overlap between the participants in t…”
ResultThe polygenic architecture of schizophrenia — rethinking pathogenesis and nosology
Smeland, O. B., Frei, O., Dale, A. M., & Andreassen, O. A. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0364-0 · Cited by 202 · see citing works
Prospects for using risk scores in polygenic medicine
Lewis, C., & Vassos, E. (2017) · Genome Medicine · doi:10.1186/s13073-017-0489-y · Cited by 172 · see citing works
“These properties, combined with the smaller number of research studies available, mean that the predictive ability of the PRS in non-European populations is currently limited [8, 10].”
BackgroundComer, A. L., Carrier, M., Tremblay, M., & Cruz‐Martín, A. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00274 · Cited by 204 · see citing works
Malaria Genomic Epidemiology Network, Band, G., Le, S. Q., Clarke, G. M., Kivinen, K., Hubbart, C., Jeffreys, A. E., Rowlands, K., Leffler, E. M., Jallow, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13480-z · Cited by 175 · see citing works
Zhao, B., Zhang, J., Ibrahim, J. G., Luo, T., Santelli, R., Li, Y., Li, T., Shan, Y., Zhu, Z., Zhou, F., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0569-z · Cited by 141 · see citing works
Ikeda, M., Takahashi, A., Kamatani, Y., Momozawa, Y., Saito, T., Kondo, K., Shimasaki, A., Kawase, K., Sakusabe, T., Iwayama, Y., et al. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby140 · Cited by 139 · see citing works
Genetic architecture of schizophrenia: a review of major advancements
Legge, S. E., Santoro, M. L., Periyasamy, S., Okewole, A., Arsalan, A., & Kowalec, K. (2021) · Psychological Medicine · doi:10.1017/s0033291720005334 · Cited by 146 · see citing works
“This locus was also reported in studies in Chinese populations (Z. Li et al., 2017; Yue et al., 2011), however, a subsequent meta-analysis of the largest East Asian schizophrenia GWAS (Lam et al., 2019) did not replicate this finding.”
Human-specific tandem repeat expansion and differential gene expression during primate evolution
Sulovari, A., Li, R., Audano, P. A., Porubskỳ, D., Vollger, M. R., Logsdon, G. A., Warren, W. C., Pollen, A. A., Chaisson, M., Eichler, E. E., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1912175116 · Cited by 131 · see citing works
“Another is GWAS SNP rs2526882, which has been recently associated with schizophrenia (51) (Dataset S12).”
BackgroundBigdeli, T. B., Genovese, G., Georgakopoulos, P., Meyers, J. L., Peterson, R. E., Iyegbe, C. O., Medeiros, H., Valderrama, J., Achtyes, E. D., Kotov, R., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0517-y · Cited by 121 · see citing works
Self-citationGenetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders
Andrade, A., Brennecke, A., Mallat, S., Brown, J., Gomez-Rivadeneira, J., Czepiel, N., & Londrigan, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143537 · Cited by 127 · see citing works
“Although a study in a Han Chinese population found no association between CACNA1D SNPs and SCZ [203], more recent studies that include larger populations of East Asian, Chinese, European and Ashkenazi Jewish individuals identified the SNP rs2358740 located in a putative promoter region for CACNA1D and the mRNA decappi…”
ResultArnau‐Soler, A., Macdonald-Dunlop, E., Adams, M. J., Clarke, T., MacIntyre, D. J., Milburn, K., Navrady, L. B., Scotland, G., Hayward, C., McIntosh, A. M., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-018-0360-y · Cited by 131 · see citing works
Ma, X., Asif, H., Dai, L., He, Y., Zheng, W., Wang, D., Ren, H., Tang, J., Li, C., Jin, K., et al. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.02.005 · Cited by 114 · see citing works
Self-citationFunctional genomics reveal gene regulatory mechanisms underlying schizophrenia risk
Huo, Y., Li, S., Liu, J., Li, X., & Luo, X. (2019) · Nature Communications · doi:10.1038/s41467-019-08666-4 · Cited by 116 · see citing works
Self-citationStevenson, A., Akena, D. H., Stroud, R. E., Atwoli, L., Campbell, M., Chibnik, L. B., Kwobah, E. K., Kariuki, S. M., Martin, A. R., de Menil, V. P., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-025469 · Cited by 112 · see citing works
Peyrot, W. J., & Price, A. L. (2021) · Nature Genetics · doi:10.1038/s41588-021-00787-1 · Cited by 106 · see citing works
Genome-wide association studies: assessing trait characteristics in model and crop plants
Alseekh, S., Kostova, D., Bulut, M., & Fernie, A. R. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03868-w · Cited by 132 · see citing works
“Among these studies risk loci for a vast number of diseases and traits, including anorexia nervosa [4], body mass index [5], cancers and their sub-types [6, 7], coronary diseases [7], inflammatory bowel disease [8], insomnia [9], type 2 diabetes mellitus [10], and schizophrenia [11], have been reported.”
BackgroundSmeland, O. B., Shadrin, A. A., Bahrami, S., Broce, I., Tesli, M., Frei, O., Wirgenes, K. V., O’Connell, K. S., Krull, F., Bettella, F., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.01.026 · Cited by 100 · see citing works
“However, among these, as many as 22 of the SCZ loci (18, 25, 27, 30, 59, 60) and eleven of the PD loci (17, 20, 41) have been associated with the disorders in subsequent GWAS analyses, supporting their role in SCZ and PD etiology.”
BackgroundInfluentialSelf-citationComprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes
Yang, C., Li, X., Wu, Y., Shen, Q., Zeng, Y., Xiong, Q., Wei, M., Chen, C., Liu, J., Huo, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03247-3 · Cited by 105 · see citing works
Self-citationEnhancer Domains Predict Gene Pathogenicity and Inform Gene Discovery in Complex Disease
Wang, X., & Goldstein, D. B. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.01.012 · Cited by 99 · see citing works
Shi, H., Burch, K. S., Johnson, R., Freund, M., Kichaev, G., Mancuso, N., Manuel, A., Dong, N., & Pasaniuc, B. (2019) · bioRxiv · doi:10.1101/858431 · Cited by 96
Weissbrod, O., Flint, J., & Rosset, S. (2018) · American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.06.002 · Cited by 95 · see citing works
Ji, G., Sun, J., Hua, Q., Zhang, L., Zhang, T., Bai, T., Wei, L., Wang, X., Qiu, B., Wang, K., et al. (2023) · Nature Mental Health · doi:10.1038/s44220-023-00111-2 · Cited by 89 · see citing works
Al-Naama, N., Mackeh, R., & Kino, T. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00032 · Cited by 88 · see citing works
Eye-brain connections revealed by multimodal retinal and brain imaging genetics
Zhao, B., Li, Y., Fan, Z., Wu, Z., Shu, J., Yang, X., Yang, Y., Wang, X., Li, B., Wang, X., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50309-w · Cited by 90 · see citing works
Self-citationCentromeric Satellite DNAs: Hidden Sequence Variation in the Human Population
Miga, K. H. (2019) · Genes · doi:10.3390/genes10050352 · Cited by 93 · see citing works
The Critical Needs and Challenges for Genetic Architecture Studies in Africa
Martin, A. R., Teferra, S., Möller, M., Hoal, E. G., & Daly, M. J. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.08.005 · Cited by 76 · see citing works
The Landscape Of Circular RNA Expression In The Human BrainPreprint
Gokoolparsadh, A., Anwar, F., & Voineagu, I. (2018) · bioRxiv · doi:10.1101/500991 · Cited by 75 · see citing works
Zamanpoor, M. (2019) · Psychiatric Genetics · doi:10.1097/ypg.0000000000000245 · Cited by 91 · see citing works
“For schizophrenia-associated loci discovered by GWAS see (Schizophrenia Working Group of the Psychiatric Genomics, 2014) and (Li et al., 2017).”
BackgroundLiu, D., Meyer, D., Fennessy, B., Feng, C., Cheng, E., Johnson, J., Park, Y. J., Rieder, M.-K., Ascolillo, S., de Pins, A. M., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01305-1 · Cited by 76 · see citing works
Self-citationEmerging evidence for astrocyte dysfunction in schizophrenia
Figueiredo, E. C. D. O., Calì, C., Petrelli, F., & Bezzi, P. (2022) · Glia · doi:10.1002/glia.24221 · Cited by 85 · see citing works
“…studies suggest that a net- work of 160 genes contribute to the etiology of the disease (Hjelm et al., 2015; Lam et al., 2019; J. Li et al., 2021; Li et al., 2017; Pardiñas et al., 2018; Periyasamy et al., 2019; Ripke et al., 2013; Rodriguez- Murillo et al., 2012; Schulmann et al., 2019; Singh…”
BackgroundGenome-wide association studies in schizophrenia: Recent advances, challenges and future perspective
Dennison, C. A., Legge, S. E., Pardiñas, A. F., & Walters, J. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.10.048 · Cited by 77 · see citing works
Vanderplow, A. M., Eagle, A. L., Kermath, B. A., Bjornson, K. J., Robison, A. J., & Cahill, M. E. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.008 · Cited by 74 · see citing works
Pruett, B. S., & Meador‐Woodruff, J. H. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.09.003 · Cited by 80 · see citing works
Wegrzyn, D., Juckel, G., & Faissner, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105482 · Cited by 73 · see citing works
Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese
Zheng, R., Li, Z., He, F., Liu, H., Chen, J., Chen, J., Xie, X., Zhou, J., Chen, H., Wu, X., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06539-w · Cited by 77 · see citing works
Self-citationHollander, J. A., Cory‐Slechta, D. A., Jacka, F. N., Szabo, S. T., Guilarte, T. R., Bilbo, S. D., Mattingly, C. J., Moy, S. S., Haroon, E., Hornig, M., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0648-5 · Cited by 70 · see citing works
Du, Y., Tan, W.-L., Chen, L., Yang, Z., Li, X.-S., Xue, X., Cai, Y.-S., & Cheng, Y. (2021) · Schizophrenia Bulletin · doi:10.1093/schbul/sbab039 · Cited by 58 · see citing works
Self-citationZhang, F., Cao, H., & Baranova, A. V. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.735136 · Cited by 54 · see citing works
“32 region, BORCS7, a genome-wide risk gene for schizophrenia (57, 58), blood pressure (59, 60), body mass index (61), and CAD (55), had the highest PIP of 0.”
BackgroundA Role for SERCA Pumps in the Neurobiology of Neuropsychiatric and Neurodegenerative Disorders
Britzolaki, A., Saurine, J., Klocke, B., & Pitychoutis, P. M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-12457-1_6 · Cited by 63 · see citing works
Recent Advances in the Genetics of Schizophrenia
Avramopoulos, D. (2018) · Complex Psychiatry · doi:10.1159/000488679 · Cited by 80 · see citing works
A genome-wide association study of outcome from traumatic brain injury
Kals, M., Kunzmann, K., Parodi, L., Radmanesh, F., Wilson, L., Izzy, S., Anderson, C. D., Puccio, A. M., Okonkwo, D. O., Temkin, N. R., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.103933 · Cited by 64 · see citing works
Rhie, S. K., Schreiner, S., Witt, H. N., Armoskus, C., Lay, F. D., Camarena, A., Spitsyna, V. N., Guo, Y., Berman, B. P., Evgrafov, O. V., et al. (2018) · Science Advances · doi:10.1126/sciadv.aav8550 · Cited by 53 · see citing works
3D genome and its disorganization in diseases
Li, R., Liu, Y., Hou, Y., Gan, J., Wu, P., & Cheng, L. (2018) · Cell Biology and Toxicology · doi:10.1007/s10565-018-9430-4 · Cited by 56 · see citing works
Self-citationGenome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort
Osborne, A. J., Pearson, J. F., Noble, A. J., Gemmell, N. J., Horwood, L. J., Boden, J. M., Benton, M. C., Macartney-Coxson, D. P., & Kennedy, M. A. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0800-3 · Cited by 47 · see citing works
A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population
Luo, N., Jing Sui （Beijing Normal University）， my correct affiliation is beijing normal university, N. Q. U. O. S. A. T., Chen, J., Zhang, F., Tian, L., Lin, D., Song, M., Calhoun, V. D., Cui, Y. J., Vergara, V. M., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.10.009 · Cited by 49 · see citing works
“The explanations could be,first, the recent ChineseHanGWAS study [82] has claimed that the high-ranking risk loci in PGC's results appear to be largely consistent between the two populations.”
ResultSelf-citationPinzón-Espinosa, J., van der Horst, M. Z., Zinkstok, J., Austin, J., Aalfs, C. M., Batalla, A., Sullivan, P. F., Vorstman, J. A. S., & Luykx, J. J. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02203-6 · Cited by 49 · see citing works
Self-citationRao, S., Baranova, A. V., Yao, Y., Wang, J., & Zhang, F. (2022) · Neuropsychobiology · doi:10.1159/000525411 · Cited by 50 · see citing works
Self-citationFolkersen, L., Pain, O., Ingason, A., Werge, T. M., Lewis, C. M., & Austin, J. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00578 · Cited by 66 · see citing works
Genetic and Epigenetic Fine Mapping of Complex Trait Associated Loci in the Human Liver
Çalışkan, M., Manduchi, E., Rao, H. S., Segert, J. A., Beltrame, M. H., Trizzino, M., Park, Y., Baker, S. W., Chesi, A., Johnson, M. E., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.05.010 · Cited by 57 · see citing works
Li, Z., Chen, P., Chen, J., Xu, Y., Wang, Q., Li, X., Li, C., He, L., & Shi, Y. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.07.037 · Cited by 45 · see citing works
“In our recent pathway enrichment analysis for schizophrenia using the largest transancestry GWAS data set (108,341 individuals) [26], the top two most significant schizophrenia-associated pathways are the regulation of insulin secretion of glucagon-like peptide 1 and the inhibition of insulin secretion by adrenaline/n…”
BackgroundMethodSelf-citationGABRB2, a key player in neuropsychiatric disorders and beyond.
Barki, M., & Xue, H. (2021) · Gene · doi:10.1016/j.gene.2021.146021 · Cited by 45 · see citing works
SZDB2.0: an updated comprehensive resource for schizophrenia research
Wu, Y., Li, X., Liu, J., Luo, X., & Yao, Y. (2020) · Human Genetics · doi:10.1007/s00439-020-02171-1 · Cited by 43 · see citing works
Self-citationWu, Y., Bi, R., Zeng, C., Ma, C., Sun, C., Li, J., Xiao, X., Li, M., Zhang, D., Zheng, P., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.05.006 · Cited by 51 · see citing works
“Because the samples in these GWAS studies were (partially) overlapped [8,11,25] or the dataset were not publically released [3–6], we focused on the result of the recent GWAS study (CLOZUK + PGC GWAS) conducted by Pardiñas et al.”
ResultSelf-citationBhome, R., Emaduddin, M., James, V., House, L. M., Thirdborough, S., Mellone, M., Tulkens, J., Primrose, J., Thomas, G. J., de Wever, O., et al. (2022) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12226 · Cited by 43 · see citing works
“B), of which only CAF-B was myofibroblastic (Li et al., 2017).”
InfluentialZhao, B., Shan, Y., Yang, Y., Yu, Z., Li, T., Wang, X., Luo, T., Zhu, Z., Sullivan, P. F., Zhao, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23130-y · Cited by 66 · see citing works
Self-citationvan Mierlo, H. C., Schot, A., Boks, M. P., & de Witte, L. D. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.05.028 · Cited by 48 · see citing works
The alterations of circular RNA expression in plasma exosomes from patients with schizophrenia
Tan, G., Wang, L., Liu, Y., Zhang, H., Feng, W., & Liu, Z. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29873 · Cited by 45 · see citing works
“Although recent reports of SZ have gained more attention (Z. Li et al., 2017; Vecera et al., 2018; Zhuo et al., 2019), the pathogenesis of SZ has been elusive.”
BackgroundSelf-citationLi, H., Qu, N., Hui, L., Cai, X. M., Zhang, C., Zhong, B., Zhang, S.-F., Chen, J., Xia, B., Wang, L., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0777-y · Cited by 44 · see citing works
Self-citationProgram, T. V. M. V., Bone, W. P., Siewert, K. M., Jha, A., Klarin, D., Damrauer, S. M., Chang, K.-M., Tsao, P. S., Assimes, T. L., Ritchie, M. D., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00773-z · Cited by 41 · see citing works
The Role of Zebrafish and Laboratory Rodents in Schizophrenia Research
Langová, V., Valeš, K., Horka, P., & Horáček, J. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00703 · Cited by 41 · see citing works
“Modeling Genetic Factors Given the very high heritability index (more than 70%) it is not surprising that more than a hundred altered genetic loci have been identified to be associated with psychosis and the number of revealed genetic factors still increases (22, 23).”
BackgroundVRK2, a Candidate Gene for Psychiatric and Neurological Disorders
Li, M., & Yue, W. (2018) · Complex Psychiatry · doi:10.1159/000493941 · Cited by 37 · see citing works
Self-citationZhang, W., Zhang, M., Xu, Z., Yan, H., Wang, H., Jiang, J., Wan, J., Tang, B., Liu, C., Chen, C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40861-2 · Cited by 45 · see citing works
“These TWAS approaches, including FUSION 8 – 10 , PrediXcan 11 , summary-data-based Mendelian randomization(SMR) 2,10,12,13 ,andjoint-tissueimputationapproachwithMendelian randomization (MR-JTI) 14 , aimed to identify the association between predictedgeneexpressionandSCZrisk.”
The genetic architecture of schizophrenia: review of large-scale genetic studies
Kato, H., Kimura, H., Kushima, I., Takahashi, N., Aleksić, B., & Ozaki, N. (2022) · Journal of Human Genetics · doi:10.1038/s10038-022-01059-4 · Cited by 47 · see citing works
“The association of this locus was confirmed in Chinese populations [60, 61]; however, the association was not replicated in the recent meta-analysis using GWASs conducted in East Asian population [62].”
ResultAmbati, A., Hillary, R. P., Leu-Semenescu, S., Ollila, H., Lin, L., During, E., Farber, N., Rico, T. J., Faraco, J., Leary, E., et al. (2021) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1101/2021.01.08.20249006 · Cited by 40
Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women
Montalvo‐Ortiz, J. L., Cheng, Z., Kranzler, H. R., Zhang, H., & Gelernter, J. E. (2019) · Scientific Reports · doi:10.1038/s41598-019-41110-7 · Cited by 45 · see citing works
The thalamus in psychosis spectrum disorder
Anticevic, A., & Halassa, M. M. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1163600 · Cited by 41 · see citing works
Liu, S., Li, A., Liu, Y., Yan, H., Wang, M., Sun, Y., Fan, L., Song, M., Xu, K., Chen, J., et al. (2019) · The British Journal of Psychiatry · doi:10.1192/bjp.2019.127 · Cited by 45 · see citing works
Self-citationZhang, Y., You, X., Li, S.-W., Long, Q., Zhu, Y., Teng, Z., & Zeng, Y. (2020) · Medical Science Monitor · doi:10.12659/msm.922426 · Cited by 36 · see citing works
Perry, B., Bowker, N., Burgess, S., Wareham, N., Upthegrove, R., Jones, P., Langenberg, C., & Khandaker, G. (2022) · Schizophrenia Bulletin Open · doi:10.1093/schizbullopen/sgac001 · Cited by 35 · see citing works
A powerful fine-mapping method for transcriptome-wide association studies
Wu, C., & Pan, W. (2019) · Human Genetics · doi:10.1007/s00439-019-02098-2 · Cited by 35 · see citing works
Evidence for cerebello-thalamo-cortical hyperconnectivity as a heritable trait for schizophrenia
Cao, H.-Y., Ingvar, M., Hultman, C., & Cannon, T. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0531-5 · Cited by 35 · see citing works
Liu, H., Sun, Y., Zhang, X., Li, S., Hu, D., Xiao, L., Chen, Y., He, L., & Wang, D. W. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00256 · Cited by 44 · see citing works
“(38), which predicted 106 causal genes for SCZ (Supplementary Table S2).”
BackgroundMethodSelf-citationLin, E., Lin, C., Lai, Y.-L., Huang, C.-H., Huang, Y.-J., & Lane, H. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00566 · Cited by 37 · see citing works
“In agreement with several previous studies (7, 22, 38–44), the current study with a small sample size didn’t demonstrate an association between the two G72 SNPs and schizophrenia.”
ResultStrawbridge, R. J., Ward, J., Lyall, L. M., Tunbridge, E. M., Cullen, B., Graham, N., Ferguson, A., Johnston, K. J. A., Lyall, D. M., Mackay, D., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0236-1 · Cited by 35 · see citing works
Self-citationWu, C., & Pan, W. (2018) · Genetics · doi:10.1534/genetics.118.300805 · Cited by 37 · see citing works
“47: 1091–1098. https://doi.org/10.1038/ng.3367 Glodzik, D., S. Morganella, H. Davies, P. T. Simpson, Y. Li et al., 2017 A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers.”
BackgroundMethodResultInfluentialGene-level analysis reveals the genetic aetiology and therapeutic targets of schizophrenia
Dang, X., Teng, Z., Yang, Y., Li, W., Liu, J., Hui, L., Zhou, D.-S., Gong, D., Dai, S.-S., Li, Y., et al. (2025) · Nature Human Behaviour · doi:10.1038/s41562-024-02091-4 · Cited by 29 · see citing works
“Specifically, for lead SNPs and potential causal variants (Supplementary Tables 2, 5, 7 and 8), we assigned candidate target genes to the variants based on the nearest gene annotated by ANNOVAR 44 (Supplementary Tables 2 and 5) and eQTL annotation results (using the BrainMeta V2 eQTL dataset)…”
Self-citationRisk of schizophrenia in relatives of individuals affected by schizophrenia: A meta-analysis
LE, L., R, K., B, M., & MJ, G. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2020.112852 · Cited by 32 · see citing works
Puvogel, S., Alsema, A. M., Kracht, L., Webster, M. J., Weickert, C. S., Sommer, I. E., & Eggen, B. J. L. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01796-0 · Cited by 34 · see citing works
Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases
Grosjean, I., Roméo, B., Domdom, M., Belaid, A., D'Andréa, G., Guillot, N., Gherardi, R., Gal, J., Milano, G., Marquette, C., et al. (2022) · Autophagy · doi:10.1080/15548627.2022.2039994 · Cited by 32 · see citing works
“The most striking findings include: i) the high polygenic nature of these diseases linked with five to seven ATG variants: For example, Alzheimer disease (PIK3C3 [26], RUBCNL [27], ZFYVE1/DFCP1 [28], WDFY3 [29], and ATG10 [30]), schizophrenia (ULK1 [31], RB1CC1 [32,33], C9orf72 [34], PIK3C3 [35], AMBRA1 [36,37], and E…”
BackgroundMcManus, I. C. (2022) · Symmetry · doi:10.3390/sym14040814 · Cited by 38 · see citing works
Consensus on potential biomarkers developed for use in clinical tests for schizophrenia
Lin, P., Sun, J., Lou, X., Li, D., Shi, Y., Li, Z., Ma, P., Li, P., Chen, S., Jin, W., et al. (2022) · General Psychiatry · doi:10.1136/gpsych-2021-100685 · Cited by 38 · see citing works
Self-citationCattaneo, A., Suderman, M., Cattane, N., Mazzelli, M., Begni, V., Maj, C., D'Aprile, I., Pariante, C., Luoni, A., Berry, A., et al. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100271 · Cited by 31 · see citing works
“In particular, two variants within the PIK3CA genomic region have been associated with schizophrenia (rs9859557 (Li et al., 2017) and rs34796896 (Pardinas et al.”
Meyers, J. L., Zhang, J., Chorlian, D. B., Pandey, A. K., Kamarajan, C., Wang, J., Wetherill, L. F., Lai, D., Chao, M. J., Chan, G., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0777-6 · Cited by 34 · see citing works
“While not much is known about these variants, rs116445911 is associated with the expression of SLC9B1 in brain [49], and SLC9B1 has been associated with schizophrenia [68], another neuropsychiatric disorder characterized by dysregulated neural connectivity [69].”
BackgroundSelf-citationZhuo, C., Zhang, Q., Wang, L., Ma, X., Li, R., Ping, J., Zhu, J., Tian, H., & Jiang, D. (2023) · CNS Drugs · doi:10.1007/s40263-023-01057-w · Cited by 40 · see citing works
“…using GWAS data from 108,341 individuals, the top two schizophrenia-associated pathways identified included glucagon-like peptide 1 (GLP-1), known to play a critical role in stimulation of insulin secretion, and adrenaline/noradrenaline which mediates inhibition of insulin secretion [19, 22].”
BackgroundMethodEtemadikhah, M., Niazi, A., Wetterberg, L., & Feuk, L. (2020) · Scientific Reports · doi:10.1038/s41598-020-57467-z · Cited by 27 · see citing works
- Authors
- Li, Z., Chen, J., Yu, H., He, L., Xu, Y., Zhang, D., Yi, Q., Li, C., Li, X., Shen, J., Song, Z., Ji, W., Wang, M., Zhou, J., Chen, B., Liu, Y., Wang, J., Wang, P., Yang, P., Wang, Q., Feng, G., Liu, B., Sun, W., Li, B., He, G., Li, W., Wan, C., Xu, Q., Li, W., Wen, Z., Liu, K., Huang, F., Ji, J., Ripke, S., Yue, W., Sullivan, P. F., O'Donovan, M. C., & Shi, Y.
- Affiliations
- Qingdao University (CN)
- Shanghai Jiao Tong University (CN)
- Peking University (CN)
- Xinjiang Medical University (CN)
- Wuhu Fourth People Hospital (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Broad Institute (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Shi, Yongyong
- ORCID
- Li, Zhiqiang
- Chen, Jianhua
- Yu, Hao
- He, Lin
- Xu, Yifeng
- Zhang, Dai
- Yi, Qizhong
- Li, Changgui
- Li, Xingwang
- Shen, Jiawei
- Song, Zhijian
- Wang, Meng
- Zhou, Juan
- Liu, Yahui
- Wang, Peng
- Yang, Ping
- Wang, Qingzhong
- Li, Baojie
- He, Guang
- Li, Weidong
- Wan, Chunling
- Xu, Qi
- Li, Wenjin
- Liu, Ke
- Huang, Fang
- Ripke, Stephan
- Yue, Weihua
- Sullivan, Patrick F
- O'Donovan, Michael C
- Shi, Yongyong
- Venue
- Nature Genetics
- Published
- 2017-10-09
- Volume
- 49
- Issue
- 11
- Pages
- 1576-1583
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2763836527
- Cited by
- 442
- References
- 0
- Citations by year
- 2026: 12 · 2025: 30 · 2024: 35 · 2023: 39 · 2022: 51 · 2021: 54 · 2020: 85 · 2019: 89 · 2018: 43 · 2017: 4
- FWCI
- 49.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Institutes of Health
- Medical Research Council (MR/P005748/1, MR/L010305/1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- schizophrenia, genetic susceptibility loci, fine mapping, Chinese population, candidate genes, genetic architecture, biological pathways
- MeSH terms
- Alleles, Chromosome Mapping, Female, Humans, Male, Schizophrenia, Genome, Human, Risk Assessment, Genetic Predisposition to Disease, Protein Interaction Mapping, Asian People, Gene Regulatory Networks, Genome-Wide Association Study, Genetic Loci
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