Association ofNKAPL,TSPAN18, andMPC2gene variants with schizophrenia based on new data and a meta-analysis in Han Chinese

2016 ◽  
Vol 29 (2) ◽  
pp. 87-94 ◽  
Author(s):  
Zhen Li ◽  
Tingting Shen ◽  
Ran Xin ◽  
Baoyun Liang ◽  
Juan Jiang ◽  
...  
Keyword(s):  
Chinese Population ◽  
Association Studies ◽  
Meta Analysis ◽  
Han Chinese ◽  
Genome Wide Association Studies ◽  
Han Chinese Population ◽  
Genotype Frequencies ◽  
Genome Wide ◽  
Significant Difference ◽  
High Heritability

BackgroundSchizophrenia (SZ) is suggested to be a complex polygenetic disorder with high heritability. Genome-wide association studies have found that the rs1635, rs11038167, and rs10489202 polymorphisms are associated with SZ in Han Chinese. However, results of validation studies are inconsistent. This study aimed to test the association between theNKAPLrs1635,TSPAN18rs11038167, andMPC2rs10489202 polymorphisms and SZ in a Chinese population.MethodsThis study contained 700 unrelated SZ patients (300 Zhuang and 400 Han) and 700 gender- and age-matched controls (300 Zhuang and 400 Han). The polymorphisms inTSPAN18(rs11038167),NKAPL(rs1635), andMPC2(rs10489202) were genotyped using the Sequenom MassARRAY method. Statistical analyses were performed with PLINK program and SPSS l6.0 for Windows. STATA11.1 was used for meta-analysis.ResultsNo statistically significant difference was found in different allele and genotype frequencies of rs1635, rs11038167, and rs10489202 between SZ cases and controls of Zhuang and Han ethnicities and the total samples (allp>0.05). Further meta-analysis suggested that single-nucleotide polymorphism rs10489202 was significantly associated with SZ in a Han Chinese population (pOR=0.002).ConclusionsOur case–control study failed to validate the significant association ofNKAPLrs1635,TSPAN18rs11038167, andMPC2rs10489202 polymorphisms with SZ susceptibility in the southern Zhuang or Han Chinese population. However, meta-analysis showed a significant association betweenMPC2variant rs10489202 and SZ susceptibility in Han Chinese.

scholarly journals Gender-Specific Association ofATP2B1Variants with Susceptibility to Essential Hypertension in the Han Chinese Population

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jin Xu ◽  
Hai-xia Qian ◽  
Su-pei Hu ◽  
Li-ya Liu ◽  
Mi Zhou ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Chinese Population ◽  
Propensity Score Analysis ◽  
Association Studies ◽  
Han Chinese ◽  
Minor Effect ◽  
Strong Linkage Disequilibrium ◽  
Genome Wide Association Studies ◽  
Han Chinese Population ◽  
Genome Wide

Previous genome-wide association studies (GWASs) found that severalATP2B1variants are associated with essential hypertension (EHT). But the “genome-wide significant”ATP2B1SNPs (rs2681472, rs2681492, rs17249754, and rs1105378) are in strong linkage disequilibrium (LD) and are located in the same LD block in Chinese populations. We asked whether there are other SNPs within theATP2B1gene associated with susceptibility to EHT in the Han Chinese population. Therefore, we performed a case-control study to investigate the association of seven tagSNPs within theATP2B1gene and EHT in the Han Chinese population, and we then analyzed the interaction among different SNPs and nongenetic risk factors for EHT. A total of 902 essential hypertensive cases and 902 normotensive controls were involved in the study. All 7 tagSNPs within theATP2B1gene were retrieved from HapMap, and genotyping was performed using the Tm-shift genotyping method. Chi-squared test, logistic regression, and propensity score analysis showed that rs17249754 was associated with EHT, particularly in females. The MDR analysis demonstrated that the interaction of rs2070759, rs17249754, TC, TG, and BMI increased the susceptibility to hypertension. Crossover analysis and stratified analysis indicated that BMI has a major effect on the development of hypertension, whileATP2B1variants have a minor effect.

scholarly journals Genome-wide association study of morbid obesity in Han Chinese

BMC Genetics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Kuang-Mao Chiang ◽  
Heng-Cheng Chang ◽  
Hsin-Chou Yang ◽  
Chien-Hsiun Chen ◽  
Hsin-Hung Chen ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Chinese Population ◽  
Association Studies ◽  
Han Chinese ◽  
Genome Wide Association ◽  
Joint Analysis ◽  
Genome Wide Association Studies ◽  
Han Chinese Population ◽  
Second Stage ◽  
Genome Wide

Abstract Background As obesity is becoming pandemic, morbid obesity (MO), an extreme type of obesity, is an emerging issue worldwide. It is imperative to understand the factors responsible for huge weight gain in certain populations in the modern society. Very few genome-wide association studies (GWAS) have been conducted on MO patients. This study is the first MO-GWAS study in the Han-Chinese population in Asia. Methods We conducted a two-stage GWAS with 1110 MO bariatric patients (body mass index [BMI] ≥ 35 kg/m2) from Min-Sheng General Hospital, Taiwan. The first stage involved 575 patients, and 1729 sex- and age-matched controls from the Taiwan Han Chinese Cell and Genome Bank. In the second stage, another 535 patients from the same hospital were genotyped for 52 single nucleotide polymorphisms (SNPs) discovered in the first stage, and 9145 matched controls from Taiwan Biobank were matched for confirmation analysis. Results The results of the joint analysis for the second stage revealed six top ranking SNPs, including rs8050136 (p-value = 7.80 × 10− 10), rs9939609 (p-value = 1.32 × 10− 9), rs1421085 (p-value = 1.54 × 10− 8), rs9941349 (p-value = 9.05 × 10− 8), rs1121980 (p-value = 7.27 × 10− 7), and rs9937354 (p-value = 6.65 × 10− 7), which were all located in FTO gene. Significant associations were also observed between MO and RBFOX1, RP11-638 L3.1, TMTC1, CBLN4, CSMD3, and ERBB4, respectively, using the Bonferroni correction criteria for 52 SNPs (p < 9.6 × 10− 4). Conclusion The most significantly associated locus of MO in the Han-Chinese population was the well-known FTO gene. These SNPs located in intron 1, may include the leptin receptor modulator. Other significant loci, showing weak associations with MO, also suggested the potential mechanism underlying the disorders with eating behaviors or brain/neural development.

scholarly journals Genome-wide Meta-analysis of Alcohol Use Disorder in East Asians

2021 ◽  
Author(s):  
Hang Zhou ◽  
Rasmon Kalayasiri ◽  
Yan Sun ◽  
Yaira Z. Nuñez ◽  
Hong-Wen Deng ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Association Studies ◽  
Meta Analysis ◽  
East Asian ◽  
Han Chinese ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
East Asians ◽  
Genome Wide

AbstractBACKGROUNDAlcohol use disorder (AUD) is a leading cause of death and disability worldwide. Genome-wide association studies (GWAS) have identified ∼30 AUD risk genes in European populations, but many fewer in East Asians.METHODSWe conducted GWAS and genome-wide meta-analysis of AUD in 13,551 subjects with East Asian ancestry, using published summary data and newly genotyped data from four cohorts: 1) electronic health record (EHR)-diagnosed AUD in the Million Veteran Program (MVP)sample; 2) DSM-IV diagnosed alcohol dependence (AD) in a Han Chinese-GSA (array) cohort;3) AD in a Han Chinese-Cyto (array) cohort; and 4) two AD datasets in a Thai cohort. The MVP and Thai samples included newly genotyped subjects from ongoing recruitment. In total, 2,254 cases and 11,297 controls were analyzed. An AUD polygenic risk score was analyzed in an independent sample with 4,464 East Asians (Kaiser Permanente data from dbGaP). Phenotypes from survey data and ICD-9-CM diagnoses were tested for association with the AUD PRS.RESULTSTwo risk loci were detected: the well-known functional variant rs1229984 in ADH1B and rs3782886 in BRAP (near the ALDH2 gene locus) are the lead variants. AUD PRS was significantly associated with days per week of alcohol consumption (beta = 0.43, se = 0.067, p = 2.47×10−10) and nominally associated with pack years of smoking (beta = 0.09, se = 0.05, p = 4.52×10−2) and ever vs. never smoking (beta = 0.06, se = 0.02, p = 1.14×10−2).CONCLUSIONSThis is the largest GWAS of AUD in East Asians to date. Building on previous findings, we were able to analyze pleiotropy, but did not identify any new risk regions, underscoring the importance of recruiting additional East Asian subjects for alcohol GWAS.

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

2019 ◽  
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.

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

BMC Medicine ◽  
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.

scholarly journals Identifying genetic variants for age of migraine onset in a Han Chinese population in Taiwan

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chia-Kuang Tsai ◽  
Chih-Sung Liang ◽  
Guan-Yu Lin ◽  
Chia-Lin Tsai ◽  
Jiunn-Tay Lee ◽  
...  
Keyword(s):  
Chinese Population ◽  
Association Studies ◽  
Asian Population ◽  
Susceptibility Genes ◽  
Han Chinese ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Significance Level ◽  
Han Chinese Population ◽  
Migraine Pathogenesis

Abstract Background Considering the involvement of genetics in migraine pathogenesis in diverse ethnic populations, genome-wide association studies (GWAS) are being conducted to identify migraine-susceptibility genes. However, limited surveys have focused on the onset age of migraine (AoM) in Asians. Therefore, in this study, we aimed to identify the susceptibility loci of migraine considering the AoM in an Asian population. Methods We conducted a GWAS in 715 patients with migraine of Han Chinese ethnicity, residing in Taiwan, to identify the susceptibility genes associated with AoM. Based on our standard demographic questionnaire, the population was grouped into different subsets. Single-nucleotide polymorphism (SNP) associations were examined using PLINK in different AoM onset groups. Results We discovered eight novel susceptibility loci correlated with AoM that reached the GWAS significance level in the Han Chinese population. First, rs146094041 in ESRRG was associated with AoM $$\le$$ ≤ 12 years. The other SNPs including rs77630941 in CUX1, rs146778855 in CDH18, rs117608715 in NOL3, rs150592309 in PRAP1, and rs181024055 in NRAP were associated with the later AoM. Conclusions To our knowledge, this is the first GWAS to investigate the AoM in an Asian Han Chinese population. Our newly discovered susceptibility genes may have prospective associations with migraine pathogenesis.

scholarly journals PGG.Han: the Han Chinese genome database and analysis platform

2019 ◽  
Vol 48 (D1) ◽  
pp. D971-D976 ◽  
Author(s):  
Yang Gao ◽  
Chao Zhang ◽  
Liyun Yuan ◽  
YunChao Ling ◽  
Xiaoji Wang ◽  
...  
Keyword(s):  
Chinese Population ◽  
Association Studies ◽  
Natural Populations ◽  
Han Chinese ◽  
Genotype Imputation ◽  
Specific Reference ◽  
Single Nucleotide Variants ◽  
Genome Database ◽  
Han Chinese Population ◽  
Genome Wide

Abstract As the largest ethnic group in the world, the Han Chinese population is nonetheless underrepresented in global efforts to catalogue the genomic variability of natural populations. Here, we developed the PGG.Han, a population genome database to serve as the central repository for the genomic data of the Han Chinese Genome Initiative (Phase I). In its current version, the PGG.Han archives whole-genome sequences or high-density genome-wide single-nucleotide variants (SNVs) of 114 783 Han Chinese individuals (a.k.a. the Han100K), representing geographical sub-populations covering 33 of the 34 administrative divisions of China, as well as Singapore. The PGG.Han provides: (i) an interactive interface for visualization of the fine-scale genetic structure of the Han Chinese population; (ii) genome-wide allele frequencies of hierarchical sub-populations; (iii) ancestry inference for individual samples and controlling population stratification based on nested ancestry informative markers (AIMs) panels; (iv) population-structure-aware shared control data for genotype-phenotype association studies (e.g. GWASs) and (v) a Han-Chinese-specific reference panel for genotype imputation. Computational tools are implemented into the PGG.Han, and an online user-friendly interface is provided for data analysis and results visualization. The PGG.Han database is freely accessible via http://www.pgghan.org or https://www.hanchinesegenomes.org.

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