Human Heredity最新文献

{"title":"Parental consanguinity and family history in relation to psoriasis and the role of sex: a case-control study.","authors":"Alanood N AlKhas, Ali H Ziyab","doi":"10.1159/000543351","DOIUrl":"https://doi.org/10.1159/000543351","url":null,"abstract":"<p><strong>Introduction: </strong>Psoriasis is caused by an interplay between intrinsic and extrinsic factors. Parental consanguinity increases homozygosity in the genome of the offspring, which in turn increases disease risk. The association between parental consanguinity and psoriasis in the offspring remains unexplored. Therefore, this study sought to evaluate the association of parental consanguinity and family history with psoriasis in the offspring, and to determine whether sex modulates the aforementioned associations.</p><p><strong>Methods: </strong>A case-control study enrolled adults aged 21 years and more. Psoriasis cases (n=139) diagnosed by dermatologists were enrolled from dermatology clinics. Controls (psoriasis-free subjects; n=278) were enrolled from workplaces. Study subjects reported information on parental consanguinity and family history of psoriasis. Logistic regression was applied to evaluate associations, and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated.</p><p><strong>Results: </strong>Cases compared to controls were more likely to report parental consanguinity (59.7% vs. 35.6%; p <0.001) and family history of psoriasis (56.8% vs. 23.7%; p <0.001). Both parental consanguinity (aOR: 2.13, 95% CI: 1.29-3.50) and family history of psoriasis (aOR: 3.43, 95% CI: 2.07-5.67) were associated with increased odds of having psoriasis. The observed association between parental consanguinity and psoriasis differed according to sex (Pinteraction = 0.008), with parental consanguinity being associated with psoriasis among males (aOR: 5.96, 95% CI: 2.39-14.82), but not among females (aOR: 1.36, 95% CI: 0.75-2.49).</p><p><strong>Conclusion: </strong>Psoriasis cases compared to controls were significantly more likely to report parental consanguinity and family history of psoriasis, with parental consanguinity being associated with psoriasis among males only.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"1-18"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Place of concordance-discordance model in evaluating NGS performance.","authors":"Yue Zhai, Claire Bardel, Maxime Vallée, Jean Iwaz, Pascal Roy","doi":"10.1159/000538401","DOIUrl":"https://doi.org/10.1159/000538401","url":null,"abstract":"<p><strong>Introduction: </strong>Ideally, evaluating NGS performance requires a gold standard; in its absence, concordance between replicates is often used as substitute standard. However, the appropriateness of the concordance-discordance criterion has been rarely evaluated. This study analyzes the relationship between the probability of discordance and the probability of error under different conditions.</p><p><strong>Methods: </strong>This study used a conditional probability approach under conditional dependence then conditional independence between two sequencing results and compares the probabilities of discordance and error in different theoretical conditions of sensitivity, specificity, and correlation between replicates, then on real results of sequencing genome NA12878. The study examines also covariate effects on discordance and error using generalized additive models with smooth functions.</p><p><strong>Results: </strong>With 99% sensitivity and 99.9% specificity under conditional independence, the probability of error for a positive concordant pair of calls is 0.1%. With additional hypotheses of 0.1% prevalence and 0.9 correlation between replicates, the probability of error for a positive concordant pair is 47.4%. With real data, the estimated sensitivity, specificity, and correlation between tests for variants are around 98.98%, 99.996%, and 93%, respectively, and the error rate for positive concordant calls approximates 2.5%. In covariate effect analyses, the effects' functional form are close between discordance and error models, though the parts of deviance explained by the covariates differ between discordance and error models.</p><p><strong>Conclusion: </strong>With conditional independence of two sequencing results, the concordance-discordance criterion seems acceptable as substitute standard. However, with high correlation, the criterion becomes questionable because a high percentage of false concordant results appears among concordant results.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of the Co-Dominance Model for Hardy-Weinberg Testing in Genetic Association Studies.","authors":"Stefan Wellek, Martina Mueller-Nurasyid, Konstantin Strauch","doi":"10.1159/000537832","DOIUrl":"https://doi.org/10.1159/000537832","url":null,"abstract":"<p><strong>Introduction: </strong>The standard way of using tests for compatibility of genetic markers with the Hardy-Weinberg equilibrium (HWE) assumptionvas a means of quality control in genetic association studies (GAS) is to vcarry out this step of preliminary data analysis with the sample of non-diseased vindividuals only. We show that this strategy has no rational basis whenever the genotype--phenotype relation for avmarker under consideration satisfies the assumption of co-dominance.</p><p><strong>Methods/results: </strong>The justification of this statement is the fact rigorously shown here that under co-dominance, the genotype distribution of a diallelic marker is in HWE among the controls if and only if the same holds true for the cases.</p><p><strong>Conclusion: </strong>The major practical consequence of that theoretical result is that under the co-dominance model, testing for HWE should be done both for cases and controls aiming to establish the combined (intersection) hypothesis of compatibility of both underlying genotype distributions with the HWE assumption. A particularly useful procedure serving this purpose is obtained through applying the confidence-interval inclusion rule derived by Wellek, Goddard and Ziegler (Biom J. 2010; 52:253-270) to both samples separately and combining these two tests by means of the intersection-union principle.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"comorbidPGS: An R Package Assessing Shared Predisposition between Phenotypes Using Polygenic Scores.","authors":"Vincent Pascat, Liudmila Zudina, Anna Ulrich, Jared G Maina, Marika Kaakinen, Igor Pupko, Amélie Bonnefond, Ayse Demirkan, Zhanna Balkhiyarova, Philippe Froguel, Inga Prokopenko","doi":"10.1159/000539325","DOIUrl":"10.1159/000539325","url":null,"abstract":"<p><strong>Introduction: </strong>Polygenic score (PGS) is a valuable method for assessing the estimated genetic liability to a given outcome or genetic variability contributing to a quantitative trait. While polygenic risk scores are widely used for complex traits, their application in uncovering shared genetic predisposition between phenotypes, i.e., when genetic variants influence more than one phenotype, remains limited.</p><p><strong>Methods: </strong>We developed an R package, comorbidPGS, which facilitates a systematic evaluation of shared genetic effects among (cor)related phenotypes using PGSs. The comorbidPGS package takes as input a set of single nucleotide polymorphisms along with their established effects on the original phenotype (Po), referred to as Po-PGS. It generates a comprehensive summary of effect(s) of Po-PGS on target phenotype(s) (Pt) with customisable graphical features.</p><p><strong>Results: </strong>We applied comorbidPGS to investigate the shared genetic predisposition between phenotypes defining elevated blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP; pulse pressure) and several cancers (breast cancer; pancreatic cancer, PanC; kidney cancer, KidC; prostate cancer, PrC; colorectal cancer, CrC) using the European ancestry UK Biobank individuals and GWAS meta-analyses summary statistics from independent set of European ancestry individuals. We report a significant association between elevated DBP and the genetic risk of PrC (β [SE] = 0.066 [0.017], p value = 9.64 × 10-5), as well as between CrC PGS and both, lower SBP (β [SE] = -0.10 [0.029], p value = 3.83 × 10-4) and lower DBP (β [SE] = -0.055 [0.017], p value = 1.05 × 10-3). Our analysis highlights two nominally significant relationships for individuals with genetic predisposition to elevated SBP leading to higher risk of KidC (OR [95% CI] = 1.04 [1.0039-1.087], p value = 2.82 × 10-2) and PrC (OR [95% CI] = 1.02 [1.003-1.041], p value = 2.22 × 10-2).</p><p><strong>Conclusion: </strong>Using comorbidPGS, we underscore mechanistic relationships between blood pressure regulation and susceptibility to three comorbid malignancies. This package offers valuable means to evaluate shared genetic susceptibility between (cor)related phenotypes through polygenic scores.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"60-70"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Novel Variants of the CAPN3 Gene in Chinese Patients with Limb-Girdle Muscular Dystrophy Recessive 1.","authors":"Lulu Zhang, Yi Zhang, Chunru Han, Juean Jiang, Jianhua Jiang, Xiuying Cai, Liqiang Yu, Huan Qi, Qi Fang, Dongxue Ding","doi":"10.1159/000539521","DOIUrl":"10.1159/000539521","url":null,"abstract":"<p><strong>Introduction: </strong>Recessive mutations in the CAPN3 gene can lead to limb-girdle muscular dystrophy recessive 1 (LGMD R1). Targeted next-generation sequencing facilitates the discovery of new mutations linked with disease, owing to its ability to selectively enrich specific genomic regions.</p><p><strong>Methods: </strong>We performed targeted next-generation sequencing of all exons of the CAPN3 gene in 4 patients with sporadic limb-girdle muscular dystrophy (LGMD) and further analyzed the effects of the novel identified variant using various software tools.</p><p><strong>Results: </strong>We found 5 variants in CAPN3 gene in 4 patients, c.82_83insC (insertion mutation) and c.1115+2T&gt;C (splicing mutation) are reported for the first time in CAPN3 (NM_000070.2). The bioinformatics analysis indicated that these two novel variants affected CAPN3 transcription as well as translation.</p><p><strong>Discussion: </strong>Our findings reveal previously unreported splicing mutation and insertion mutation in CAPN3 gene, further expanding the pathogenic gene profile of LGMD.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"52-59"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for Mitochondrial tRNA Variants in 200 Patients with Systemic Lupus Erythematosus.","authors":"Dan Xuan, Fuyong Qiang, Hui Xu, Li Wang, Yonghui Xia","doi":"10.1159/000542357","DOIUrl":"10.1159/000542357","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic lupus erythematosus (SLE) is a common autoimmune disease with unknown etiology. Recently, a growing number of evidence suggested that mitochondrial dysfunctions played active roles in the pathogenesis of SLE, but its detailed mechanism remains largely undetermined. The aim of this study was to analyze the frequencies of mitochondrial tRNA (mt-tRNA) variants in Chinese individuals with SLE.</p><p><strong>Methods: </strong>We carried out a mutational screening of mt-tRNA variants in a cohort of 200 patients with SLE and 200 control subjects by PCR-Sanger sequencing. The potential pathogenicity of mt-tRNA variants was evaluated by phylogenetic conservation and haplogroup analyses. In addition, trans-mitochondrial cybrid cell lines were established, and mitochondrial functions including ATP, reactive oxygen species (ROS), mitochondrial DNA (mtDNA) copy number, mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and mt-RNA transcription were analyzed in cybrids with and without these putative pathogenic mt-tRNA variants.</p><p><strong>Results: </strong>We identified five possible pathogenic variants: tRNAVal G1606A, tRNALeu(UUR) A3243G, tRNAIle A4295G, tRNAGly T9997C, and tRNAThr A15924G that only found in SLE patients but were absent in controls. Interestingly, these variants were located at extremely conserved nucleotides of the corresponding tRNAs and may alter tRNAs' structure and function. Furthermore, cells carrying these tRNA variants had much lower levels of ATP, mtDNA copy number, MMP, and SOD than controls; by contrast, the levels of ROS increased significantly (p < 0.05 for all). Furthermore, a significant reduction in mt-ND1, ND2, ND3, ND5, and A6 mRNA expression was observed in cells with these mt-tRNA variants, while compared with controls. Thus, failures in tRNA metabolism caused by these variants would impair mitochondrial translation and subsequently lead to mitochondrial dysfunction that was involved in the progression and pathogenesis of SLE.</p><p><strong>Conclusions: </strong>Our study suggested that mt-tRNA variants were important causes for SLE, and screening for mt-tRNA pathogenic variants was recommended for early detection and prevention for this disorder.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"84-97"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint Linkage and Association Analysis Using GENEHUNTER-MODSCORE with an Application to Familial Pancreatic Cancer.","authors":"Markus Brugger, Manuel Lutz, Martina Müller-Nurasyid, Peter Lichtner, Emily P Slater, Elvira Matthäi, Detlef K Bartsch, Konstantin Strauch","doi":"10.1159/000535840","DOIUrl":"10.1159/000535840","url":null,"abstract":"<p><strong>Introduction: </strong>Joint linkage and association (JLA) analysis combines two disease gene mapping strategies: linkage information contained in families and association information contained in populations. Such a JLA analysis can increase mapping power, especially when the evidence for both linkage and association is low to moderate. Similarly, an association analysis based on haplotypes instead of single markers can increase mapping power when the association pattern is complex.</p><p><strong>Methods: </strong>In this paper, we present an extension to the GENEHUNTER-MODSCORE software package that enables a JLA analysis based on haplotypes and uses information from arbitrary pedigree types and unrelated individuals. Our new JLA method is an extension of the MOD score approach for linkage analysis, which allows the estimation of trait-model and linkage disequilibrium (LD) parameters, i.e., penetrance, disease-allele frequency, and haplotype frequencies. LD is modeled between alleles at a single diallelic disease locus and up to three diallelic test markers. Linkage information is contributed by additional multi-allelic flanking markers. We investigated the statistical properties of our JLA implementation using extensive simulations, and we compared our approach to another commonly used single-marker JLA test. To demonstrate the applicability of our new method in practice, we analyzed pedigree data from the German National Case Collection for Familial Pancreatic Cancer (FaPaCa).</p><p><strong>Results: </strong>Based on the simulated data, we demonstrated the validity of our JLA-MOD score analysis implementation and identified scenarios in which haplotype-based tests outperformed the single-marker test. The estimated trait-model and LD parameters were in good accordance with the simulated values. Our method outperformed another commonly used JLA single-marker test when the LD pattern was complex. The exploratory analysis of the FaPaCa families led to the identification of a promising genetic region on chromosome 22q13.33, which can serve as a starting point for future mutation analysis and molecular research in pancreatic cancer.</p><p><strong>Conclusion: </strong>Our newly proposed JLA-MOD score method proves to be a valuable gene mapping and characterization tool, especially when either linkage or association information alone provide insufficient power to identify the disease-causing genetic variants.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"8-31"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Recessive Effects of Coding Variants on Common Clinical Phenotypes in Exome-Sequenced UK Biobank Participants.","authors":"David Curtis","doi":"10.1159/000537771","DOIUrl":"10.1159/000537771","url":null,"abstract":"<p><strong>Introduction: </strong>Previous studies have demonstrated effects of rare coding variants on common, clinically relevant phenotypes although the additive burden of these variants makes only a small contribution to overall trait variance. Although recessive effects of individual homozygous variants have been studied, little work has been done to elucidate the impact of rare coding variants occurring together as compound heterozygotes.</p><p><strong>Methods: </strong>In this study, attempts were made to identify pairs of variants likely to be occurring as compound heterozygotes using 200,000 exome-sequenced subjects from the UK Biobank. Pairs of variants, which were seen together in the same subject more often than would be expected by chance, were excluded as it was assumed that these might be present in the same haplotype. Attention was restricted to variants with minor allele frequency ≤0.05 and to those predicted to alter amino acid sequence or prevent normal gene expression. For each gene, compound heterozygotes were assigned scores based on the rarity and predicted functional consequences of the constituent variants and the scores were used in a logistic regression analysis to test for association with hypertension, hyperlipidaemia, and type 2 diabetes.</p><p><strong>Results: </strong>No statistically significant associations were observed and the results conformed to the distribution, which would be expected under the null hypothesis. The average number of apparently compound heterozygous subjects for each gene was only 282.2.</p><p><strong>Conclusion: </strong>It seems difficult to detect an effect of compound heterozygotes on the risk of these phenotypes. Even if recessive effects from compound heterozygotes do occur, they would only affect a small number of people and overall would not make a substantial contribution to phenotypic variance. This research has been conducted using the UK Biobank Resource.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"1-7"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Statistical Testing Strategy Accounting for Random and Nonrandom (Skewed) X-Chromosome Inactivation Identifies Lung Cancer Susceptibility Loci among Smokers.","authors":"Rodolphe Jantzen, Sophie Camilleri-Broët, Nicole Ezer, Philippe Broët","doi":"10.1159/000539520","DOIUrl":"10.1159/000539520","url":null,"abstract":"<p><strong>Introduction: </strong>Lung cancer is the most common cancer worldwide in mortality and the second in incidence. Epidemiological studies found a higher lung cancer risk for smoking women in comparison to men, but these sex differences, irrespective of smoking habits, remain controversial. One of the hypotheses concerns the genetic contribution of the sex chromosomes. However, while genome-wide association studies identified many lung cancer susceptibility loci, these analyses have excluded X-linked loci.</p><p><strong>Methods: </strong>To account for nongenetic factors, we first presented an association test based on an additive-multiplicative hazard model accounting for random/nonrandom X-inactivation process. A simulation study was performed to investigate the properties of the proposed test as compared with the Wald test from a Cox model with random X-inactivation process and the partial likelihood ratio test proposed by Xu et al. accounting for nonrandom X-inactivation process. Then, we performed an X chromosome-wide association study on 9,261 individuals from the population-based cohort CARTaGENE to identify susceptibility loci for lung cancer among current and past smokers. We adjusted for the PLCOm2012 lung cancer risk score used in screening programs.</p><p><strong>Results: </strong>Simulation results show the good behavior of the proposed test in terms of power and type I error probability as compared to the Xu et al. and the Wald test. Using the proposed test statistic and adjusting for the PLCOm2012 score, the X chromosome-wide statistical analysis identified two SNPs in low-linkage disequilibrium located in the IL1RAPL1 (IL-1 R accessory protein-like) gene: rs12558491 (p = 2.75×10-9) and rs12835699 (p = 1.26×10-6). For both SNPs, the minor allele was associated with lower lung cancer risk. Adjusting for multiple testing, no signal was detected using the Wald or the Xu et al. likelihood ratio tests.</p><p><strong>Conclusion: </strong>By taking into account smoking behavior and the X-inactivation process, the investigation of the X chromosome has shed a new light on the association between X-linked loci and lung cancer. We identified two loci associated with lung cancer located in the IL1RAPL1 gene. This finding would have been overlooked by examining only results from other test statistics.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"71-83"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Hypoxia-Related Signature as Candidate Detector for Schizophrenia Based on Genome-Wide Gene Expression.","authors":"Zhitao Li, Xinyu Sun, Jia He, Dongyan Kong, Jinyi Wang, Lili Wang","doi":"10.1159/000529902","DOIUrl":"10.1159/000529902","url":null,"abstract":"<p><strong>Introduction: </strong>Schizophrenia (SCZ), a severe neuropsychiatric disorder with high genetic susceptibility, has high rates of misdiagnosis due to the unavoidably subjective factors and heterogeneous clinical presentations. Hypoxia has been identified as an importantly risk factor that participates in the development of SCZ. Therefore, development of a hypoxia-related biomarker for SCZ diagnosis is promising. Therefore, we dedicated to develop a biomarker that could contribute to distinguishing healthy controls and SCZ patients.</p><p><strong>Methods: </strong>GSE17612, GSE21935, and GSE53987 datasets, consisting of 97 control samples and 99 SCZ samples, were involved in our study. The hypoxia score was calculated based on the single-sample gene-set enrichment analysis using the hypoxia-related differentially expressed genes to quantify the expression levels of these genes for each SCZ patient. Patients in high-score groups were defined if their hypoxia score was in the upper half of all hypoxia scores and patients in low-score groups if their hypoxia score was in the lower half. GSEA was applied to detect the functional pathway of these differently expressed genes. CIBERSORT algorithm was utilized to evaluate the tumor-infiltrating immune cells of SCZ patients.</p><p><strong>Results: </strong>In this study, we developed and validated a biomarker consisting of 12 hypoxia-related genes that could distinguish healthy controls and SCZ patients robustly. We found that the metabolism reprogramming might be activated in the patient with high hypoxia score. Finally, CIBERSORT analysis illustrated that lower composition of naive B cells and higher composition of memory B cells might be observed in low-score groups of SCZ patients.</p><p><strong>Conclusion: </strong>These findings revealed that the hypoxia-related signature was acceptable as a detector for SCZ, providing further insight into effective diagnosis and treatment strategies for SCZ.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"18-28"},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10124753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9352414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}