Loci with genome-wide associations with schizophrenia in the Han Chinese population

BackgroundA large schizophrenia genome-wide association study (GWAS) and a subsequent extensive replication study of individuals of European ancestry identified eight new loci with genome-wide significance and suggested that theMIR137-mediated pathway plays a role in the predisposition for schizophrenia.AimsTo validate the above findings in a Han Chinese population.MethodWe analysed the single nucleotide polymorphisms (SNPs) in the newly identified schizophrenia candidate loci and predictedMIR137target genes based on our published Han Chinese populations (BIOX) GWAS data. We then analysed 18 SNPs from the candidate regions in an independent cohort that consisted of 3585 patients with schizophrenia and 5496 controls of Han Chinese ancestry.ResultsWe replicated the associations of five markers (P<0.05), including three that were located in the predictedMIR137target genes. Two loci (ITIH3/4: rs2239547,P=1.17×10–10andCALN1: rs2944829,P=9.97×10–9) exhibited genome-wide significance in the Han Chinese population.ConclusionsTheITIH3/4locus has been reported to be of genome-wide significance in the European population. The successful replication of this finding in a different ethnic group provides stronger evidence for the association between schizophrenia andITIH3/4. We detected the first genome-wide significant association of schizophrenia withCALN1, which is a predicted target ofMIR137, and thus provide new evidence for the associations betweenMIR137targets and schizophrenia.

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Association between Ocular Axial Length-Related Genes and High Myopia in a Han Chinese Population

Ophthalmologica ◽

10.1159/000439446 ◽

2015 ◽

Vol 235 (1) ◽

pp. 57-60 ◽

Cited By ~ 10

Author(s):

Ya-Ting Li ◽

Ming-Kun Xie ◽

Jin Wu

Keyword(s):

Axial Length ◽

Genetic Variants ◽

Chinese Population ◽

High Myopia ◽

Genome Wide Association Study ◽

Han Chinese ◽

Nucleotide Polymorphisms ◽

Han Chinese Population ◽

Functional Roles ◽

Genome Wide

Aims: A previous genome-wide association study of high myopia identified five genome-wide loci for ocular axial length (C3orf26, ZC3H11B, RSPO1, GJD2, and ZNRF3). The aim of our study was to investigate the association between high myopia and genetic variants in the five loci in Han Chinese subjects. Methods: Five single nucleotide polymorphisms were genotyped in 296 unrelated high-myopia subjects and 300 matched emmetropic controls by the SNaPshot method. The distribution of genotypes in the cases and controls was compared in codominant, dominant, and recessive genetic models by using SNPStats online software. Results: Significant associations between rs994767 near ZC3H11B (p = 0.001), rs4074961 in RSPO1 (p < 0.001), and rs11073058 in GJD2 (p = 0.029) and high myopia were observed. Odds ratios (95% confidence intervals) were 1.532 (1.200-1.955), 1.603 (1.267-2.029), and 1.290 (1.027-1.621) for the rs994767 T allele, rs4074961 T allele, and rs11073058 T allele, respectively. But rs9811920 in C3orf26 and rs12321 in ZNRF3 were not associated with high myopia. Conclusion: Our findings suggested that genetic variants in ZC3H11B, RSPO1, and GJD2 are associated with susceptibility to the development of high myopia in a Han Chinese population. Functional roles of ZC3H11B, RSPO1, and GJD2 in the pathology of high myopia need to be further investigated.

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Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.144576 ◽

2011 ◽

Vol 70 (10) ◽

pp. 1793-1797 ◽

Cited By ~ 11

Author(s):

Patrick Danoy ◽

Meng Wei ◽

Hadler Johanna ◽

Lei Jiang ◽

Dongyi He ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Association Study ◽

Chinese Population ◽

Genome Wide Association Study ◽

Susceptibility Genes ◽

Han Chinese ◽

European Ancestry ◽

Nucleotide Polymorphisms ◽

Two Phase ◽

Han Chinese Population

BackgroundThe genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations.ObjectiveTo investigate these associations in the Han Chinese population.MethodsHaplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r2=0.8) across 19 distinct RA genomic regions. A two phase case–control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p<0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied.ResultsRobust association was detected for MMEL1 and CTLA4, and modest association was identified for another six loci: PADI4, STAT4, PRDM1, CDK6, TRAF1-C5 and KIF5A-PIP4K2C. All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6×10−5 unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4, significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3×10−5 unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed.ConclusionThis study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.

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East Asian Genome-wide association study derived loci in relation to type 2 diabetes in the Han Chinese population

Acta Biochimica Polonica ◽

10.18388/abp.2018_2632 ◽

2019 ◽

Cited By ~ 1

Author(s):

Sijia Zhang ◽

Esma Jamaspishvili ◽

Huixin Tong ◽

Yongjie Chen ◽

Zhongyu Zhou ◽

...

Keyword(s):

Type 2 Diabetes ◽

Chinese Population ◽

Genome Wide Association Study ◽

Meta Analysis ◽

East Asian ◽

Repetitive Sequences ◽

Han Chinese ◽

Han Chinese Population ◽

Genome Wide

Meta-analysis of GWAS in East Asian populations had established 10 loci that were associated with type 2 diabetes. Eight of them were with genome-wide significance and two with a border line association. Since these data have not been studied in an independent Han Chinese population, we aimed to investigate the association of these susceptibility loci with type 2 diabetes in an independent Han Chinese population. We executed a case-control study in 2 000 Chinese by the SNPscan method. Firstly, the repetitive sequences of 10 loci were assessed. Next, we investigated the association of 8 SNPs out of 10 with type 2 diabetes and constructed the GRS of those 8 SNPs. Finally, the relationship of the 8 loci and diabetes-related traits was analyzed. Based on the fact, that highly repetitive sequences were detected in 2 SNPs, we investigated the remaining 8 SNPs. With the exception of four SNPs (CMIP rs16955379, PEPD rs3786897, PSMD6 rs831571, ZFAND3 rs9470794), the other SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports, especially GLIS3 rs7041847 and KCNK16 rs1535500 were significantly associated with type 2 diabetes (rs1535500: p=0.005, OR=1.224, 95% CI 1.062–1.409; rs7041847: p=0.035, OR=1.118, 95% CI 1.070–1.388). The GRS constructed from the 8 SNPs was significantly associated with type 2 diabetes in the Chinese population (p=0.004, OR=1.065, 95% CI: 1.021–1.111). Among the participants with 24≤BMI<28 kg/m2 the 8 SNPs were significantly associated with type 2 diabetes (p=0.040, OR=1.079, 95% CI: 1.003–1.160). In quantitative trait analyses, WWOX rs17797882 was associated with decreased HOMA-β and increased level of TG and HDL-Ch, while PEPD rs3786897 and MAEA rs6815464 were associated with decreased fasting plasma glucose, and KCNK16 rs1535500 has shown a significant association with increased T-Ch and PSMD6 rs831571 had a significant association with decreased HDL-Ch. In Conclusion, with high probability the 8 loci identified in the East Asian GWAS meta-analysis are associated with type 2 diabetes in the Han Chinese population.

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Faculty Opinions recommendation of Genome-wide association study of bipolar I disorder in the Han Chinese population.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3012962.2692060 ◽

2010 ◽

Author(s):

Annette Dolphin

Keyword(s):

Association Study ◽

Chinese Population ◽

Genome Wide Association Study ◽

Han Chinese ◽

Genome Wide Association ◽

Bipolar I Disorder ◽

Han Chinese Population ◽

Genome Wide

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A Genome-Wide Association Study Finds Variants at 2p21 Associated with Self-Reported Sensitive Skin in the Han Chinese population

Journal of Investigative Dermatology ◽

10.1016/j.jid.2021.04.021 ◽

2021 ◽

Author(s):

Bingjie Li ◽

Xiyang Cai ◽

Lizhong Wang ◽

Jiarui Li ◽

Ying Zou ◽

...

Keyword(s):

Association Study ◽

Chinese Population ◽

Genome Wide Association Study ◽

Han Chinese ◽

Genome Wide Association ◽

Sensitive Skin ◽

Han Chinese Population ◽

Genome Wide ◽

A Genome

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Genome-wide association study of bipolar I disorder in the Han Chinese population

Molecular Psychiatry ◽

10.1038/mp.2010.43 ◽

2010 ◽

Vol 16 (5) ◽

pp. 548-556 ◽

Cited By ~ 103

Author(s):

M T M Lee ◽

C H Chen ◽

C S Lee ◽

C C Chen ◽

M Y Chong ◽

...

Keyword(s):

Association Study ◽

Chinese Population ◽

Genome Wide Association Study ◽

Han Chinese ◽

Genome Wide Association ◽

Bipolar I Disorder ◽

Han Chinese Population ◽

Genome Wide

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Identification of Novel Susceptibility Loci for Kawasaki Disease in a Han Chinese Population by a Genome-Wide Association Study

PLoS ONE ◽

10.1371/journal.pone.0016853 ◽

2011 ◽

Vol 6 (2) ◽

pp. e16853 ◽

Cited By ~ 71

Author(s):

Fuu-Jen Tsai ◽

Yi-Ching Lee ◽

Jeng-Sheng Chang ◽

Li-Min Huang ◽

Fu-Yuan Huang ◽

...

Keyword(s):

Kawasaki Disease ◽

Association Study ◽

Chinese Population ◽

Genome Wide Association Study ◽

Han Chinese ◽

Genome Wide Association ◽

Susceptibility Loci ◽

Han Chinese Population ◽

Genome Wide ◽

A Genome

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Genome-wide association study followed by trans-ancestry meta-analysis identify 17 new risk loci for schizophrenia

BMC Medicine ◽

10.1186/s12916-021-02039-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jiewei Liu ◽

Shiwu Li ◽

Xiaoyan Li ◽

Wenqiang Li ◽

Yongfeng Yang ◽

...

Keyword(s):

Association Study ◽

Chinese Population ◽

Meta Analysis ◽

Han Chinese ◽

Genome Wide Association ◽

European Ancestry ◽

Polygenic Risk Score ◽

Summary Statistics ◽

Han Chinese Population ◽

Genome Wide

Abstract Background Over 200 schizophrenia risk loci have been identified by genome-wide association studies (GWASs). However, the majority of risk loci were identified in populations of European ancestry (EUR), potentially missing important biological insights. It is important to perform 5 GWASs in non-European populations. Methods To identify novel schizophrenia risk loci, we conducted a GWAS in Han Chinese population (3493 cases and 4709 controls). We then performed a large-scale meta-analysis (a total of 143,438 subjects) through combining our results with previous GWASs conducted in EAS and EUR. In addition, we also carried out comprehensive post-GWAS analysis, including heritability partitioning, enrichment of schizophrenia associations in tissues and cell types, trancscriptome-wide association study (TWAS), expression quantitative trait loci (eQTL) and differential expression analysis. Results We identified two new schizophrenia risk loci, including associations in SHISA9 (rs7192086, P = 4.92 × 10-08) and PES1 (rs57016637, P = 2.33 × 10−11) in Han Chinese population. A fixed-effect meta-analysis (a total of 143,438 subjects) with summary statistics from EAS and EUR identifies 15 novel genome-wide significant risk loci. Heritability partitioning with linkage disequilibrium score regression (LDSC) reveals a significant enrichment of schizophrenia heritability in conserved genomic regions, promoters, and enhancers. Tissue and cell-type enrichment analyses show that schizophrenia associations are significantly enriched in human brain tissues and several types of neurons, including cerebellum neurons, telencephalon inhibitory, and excitatory neurons. Polygenic risk score profiling reveals that GWAS summary statistics from trans-ancestry meta-analysis (EAS + EUR) improves prediction performance in predicting the case/control status of our sample. Finally, transcriptome-wide association study (TWAS) identifies risk genes whose cis-regulated expression change may have a role in schizophrenia. Conclusions Our study identifies 17 novel schizophrenia risk loci and highlights the importance and necessity of conducting genetic study in different populations. These findings not only provide new insights into genetic etiology of schizophrenia, but also facilitate to delineate the pathophysiology of schizophrenia and develop new therapeutic targets.

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