The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.
Comparative genetic architectures of schizophrenia in East Asian and European populations
Open accessPublished version of a preprint
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“A recent genome-wide association study (GWAS) reported 176 genomic loci containing common alleles associated with schizophrenia9”
From Mapping genomic loci implicates genes and synaptic biology in schizophrenia (2022) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“In the field of mental health, specifically concerning schizophrenia, a meta-analysis found that risk-flagging models trained on European populations have reduced performance in East Asian populations [88].”
From Barriers to and facilitators of artificial intelligence adoption in health care: scoping review (2024) · cites this paper as [88]
The cited source says what the claim attributes to it.
In the citing paper
“Previous studies have found that population diversity may improve fine-mapping resolution38,39”
From Shared genetic architectures of educational attainment in East Asian and European populations (2024) · cites this paper as [38]
In the citing paper
“For almost all cohorts, PRS had more explanatory power based on risk alleles derived from the larger combined ancestry GWAS than from the matched ancestry GWAS; given the ancestry specific sample sizes, unsurprisingly9, this effect was strongest for the non-EUR samples”
From Mapping genomic loci implicates genes and synaptic biology in schizophrenia (2022) · cites this paper as [9]
In the citing paper
“PRS explained most variance in liability in cohorts of European ancestry (again a result of the ancestry composition of the GWAS9) and in samples which by ascertainment likely include the most severe cases (hospitalised patients or those treated with clozapine)”
From Mapping genomic loci implicates genes and synaptic biology in schizophrenia (2022) · cites this paper as [9]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Self-citationESTIMATING F -STATISTICS FOR THE ANALYSIS OF POPULATION STRUCTURE
Weir, B. S., & Cockerham, C. C. (1984) · Evolution · doi:10.1111/j.1558-5646.1984.tb05657.x · Cited by 18,909
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247
Self-citationBorenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2009) · doi:10.1002/9780470743386 · Cited by 14,225
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2021) · doi:10.1002/9781119558378 · Cited by 9,799
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
Self-citationMolecular signatures database (MSigDB) 3.0
Liberzon, A., Subramanian, A., Pinchback, R., Thorvaldsdóttir, H., Tamayo, P., & Mesirov, J. P. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr260 · Cited by 7,111
LD 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
Self-citationMETAL: fast and efficient meta-analysis of genomewide association scans
Willer, C. J., Li, Y., & Abecasis, G. R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq340 · Cited by 5,205
Cited by
Sorted by citations
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
Self-citationClinical 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 2,821
Self-citationGenome-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
Self-citationPolygenic risk scores: from research tools to clinical instruments
Lewis, C. M., & Vassos, E. (2020) · Genome Medicine · doi:10.1186/s13073-020-00742-5 · Cited by 1,360
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
Self-citation
Metadata
- Authors
- 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., Ikeda, M., Benyamin, B., Brown, B. C., Liu, R., Zhou, W., Guan, L., Kamatani, Y., Kim, S.-W., Kubo, M., Kusumawardhani, A. A. A. A., Liu, C.-M., Ma, H., Periyasamy, S., Takahashi, A., Xu, Z., Yu, H., Zhu, F., Chen, W. J., Faraone, S., Glatt, S. J., He, L., Hyman, S. E., Hwu, H.-G., McCarroll, S. A., Neale, B. M., Sklar, P., Wildenauer, D. B., Yu, X., Zhang, D., Mowry, B. J., Lee, J., Holmans, P., Xu, S., Sullivan, P. F., Ripke, S., O’Donovan, M. C., Daly, M. J., Qin, S., Sham, P., Iwata, N., Hong, K. S., Schwab, S. G., Yue, W., Tsuang, M., Liu, J., Ma, X., Kahn, R. S., Shi, Y., & Huang, H.
- Affiliations
- Broad Institute (US)
- Qingdao University (CN)
- Karolinska Institutet (SE)
- Shanghai Institute of Nutrition and Health (CN)
- Fujita Health University (JP)
- The University of Queensland (AU)
- New York Genome Center (US)
- Shanghai Jiao Tong University (CN)
- Peking University (CN)
- RIKEN Center for Integrative Medical Sciences (JP)
- Chonnam National University (KR)
- University of Indonesia (ID)
- National Taiwan University (TW)
- National Cerebral and Cardiovascular Center (JP)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- State University of New York (US)
- SUNY Upstate Medical University (US)
- Jinan University (CN)
- Icahn School of Medicine at Mount Sinai (US)
- The University of Western Australia (AU)
- Institute of Mental Health (SG)
- Cardiff University (GB)
- Chinese Academy of Sciences (CN)
- University of North Carolina at Chapel Hill (US)
- University of Hong Kong (HK)
- Samsung Medical Center (KR)
- University of Wollongong (AU)
- University of California San Diego (US)
- National University of Singapore (SG)
- University Medical Center Utrecht (NL)
- Corresponding author
- Ma, Xixian
- Yue, Weihua
- Tsuang, Ming
- Liu, Jianjun
- Ma, Xiancang
- Kahn, René S.
- Shi, Yongyong
- Huang, Hailiang
- ORCID
- Lam, Max
- Chen, Chia-Yen
- Li, Zhiqiang
- Martin, Alicia R.
- Bryois, Julien
- Ma, Xixian
- Gaspar, Helena
- Ikeda, Masashi
- Benyamin, Beben
- Brown, Brielin C.
- Kamatani, Yoichiro
- Kim, Sung-Wan
- Kubo, Michiaki
- Liu, Chih-Min
- Periyasamy, Sathish
- Takahashi, Atsushi
- Yu, Hao
- Chen, Wei J.
- Faraone, Stephen
- Glatt, Stephen J.
- Hyman, Steven E.
- Hwu, Hai-Gwo
- McCarroll, Steven A.
- Neale, Benjamin M.
- Sklar, Pamela
- Wildenauer, Dieter B.
- Mowry, Bryan J.
- Lee, Jimmy
- Holmans, Peter
- Xu, Shuhua
- Sullivan, Patrick F.
- Ripke, Stephan
- O’Donovan, Michael C.
- Daly, Mark J.
- Qin, Shengying
- Sham, Pak
- Iwata, Nakao
- Hong, Kyung S.
- Schwab, Sibylle G.
- Yue, Weihua
- Tsuang, Ming
- Kahn, René S.
- Shi, Yongyong
- Huang, Hailiang
- Venue
- Nature Genetics
- Published
- 2019-11-18
- Volume
- 51
- Issue
- 12
- Pages
- 1670-1678
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC6885121
- OpenAlex
- W2983765585
- Cited by
- 655
- References
- 93
- Citations by year
- 2026: 46 · 2025: 102 · 2024: 103 · 2023: 113 · 2022: 113 · 2021: 94 · 2020: 72 · 2019: 11
- FWCI
- 57.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Medical Research Council (MR/P005748/1, MR/L010305/1)
- Japan Society for the Promotion of Science (17H04251)
- National Institute of Mental Health (U01MH109539, U01MH109514, R01MH085521, U01MH109528, R01MH085560, U01MH109536, K99MH117229, U01MH109532)
- National Human Genome Research Institute (U54HG003067)
- National Institute of Allergy and Infectious Diseases (R21AI139012)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK114379)
- 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 architecture, East Asian ancestry, European ancestry, polygenic risk score, genetic correlation, novel genetic loci, cross-population generalizability, genome-wide association study
- MeSH terms
- Asia, Eastern, Genetics, Population, Humans, Schizophrenia, Case-Control Studies, Polymorphism, Single Nucleotide, White People, Asian People, Genome-Wide Association Study
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
