{"title":"Exploration of shared diagnostic genes and mechanisms between crohn's disease and ischemic stroke by integrated comprehensive bioinformatics analysis and machine learning.","authors":"Chunlin Ren, Xinmin Li, Fangjie Yang, Jing Wang, Pengxue Guo, Zhenfei Duan, Yuting Kong, Mengyao Bi, Yongqi Yuan, Tian Tian, Yasu Zhang","doi":"10.1007/s00335-025-10145-9","DOIUrl":"10.1007/s00335-025-10145-9","url":null,"abstract":"<p><p>Investigating comorbidities of ischemic stroke (IS) enhances understanding of its intricate mechanisms. Crohn's disease (CD) is associated with an increased risk of IS, but the underlying mechanisms remain unclear. This study aims to identify shared diagnostic genes and explore the mechanisms underlying CD-IS comorbidity using bioinformatics and machine learning approaches. Gene expression data for CD and IS were obtained from the Gene Expression Omnibus. Shared genes were identified through differential expression and weighted gene co-expression network analyses (WGCNA). Functional enrichment analyses highlighted key biological pathways. Core genes were screened via machine learning algorithms and protein-protein interaction networks. Diagnostic nomograms were constructed, and single-cell RNA sequencing was used to characterize expression patterns of core genes. Immune cell infiltration was quantified using CIBERSORT, and a competing endogenous RNA network was built based on TarBase and SpongeScan databases. Mendelian randomization was performed to assess causal associations between core genes and disease risk. Candidate drugs were predicted using the Drug-Gene Interaction Database and validated through molecular docking. Twenty shared genes were identified through differential expression analysis and WGCNA. The toll-like receptor (TLR) signaling pathway was identified as a key pathway in CD-IS comorbidity. TLR2 and TLR8 were identified as core genes, with strong diagnostic performance (AUC > 0.80). The polymorphism of rs73221365 was associated with both CD and IS. Resveratrol hexanoic acid was a potential therapeutic candidate for CD-IS comorbidity. This study highlights the critical role of TLR-mediated inflammatory responses in CD-IS comorbidity. TLR2 and TLR8 may serve as promising diagnostic biomarkers. These findings advance understanding of the shared pathophysiology in CD-IS comorbidity and provide a foundation for developing precise diagnostics and targeted therapies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"973-991"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528637","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}
Mammalian GenomePub Date : 2025-09-01Epub Date: 2025-06-24DOI: 10.1007/s00335-025-10143-x
Abdul Basit, Anjing Liu, Wanglong Zheng, Jianzhong Zhu
{"title":"A review on the mechanism and potential diagnostic application of CRISPR/Cas13a system.","authors":"Abdul Basit, Anjing Liu, Wanglong Zheng, Jianzhong Zhu","doi":"10.1007/s00335-025-10143-x","DOIUrl":"10.1007/s00335-025-10143-x","url":null,"abstract":"<p><p>Clustered regularly Interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins form a natural immune defense system in prokaryotic species, with approximately 90% of archaea and 40% of bacteria possessing these systems, highlighting their widespread role in microbial immunity. Among these, the CRISPR/Cas13a system, guided by a single-stranded RNA (crRNA), selectively targets RNA sequences and has shown immense potential in developing sensitive diagnostic tools. Recent advancements have combined Cas13a with amplification methods and lateral flow detection (CRISPR/Cas13a-LFD), improving its application for rapid and accurate RNA detection. In this review, we explore the history, structure, and functional mechanism of the CRISPR/Cas13a system, focusing on its diagnostic capabilities. We compare CRISPR/Cas13a to conventional diagnostic approaches, highlighting their advantages in sensitivity, specificity, speed, and flexibility for point-of-care application. Given the rapid development of CRISPR-based diagnostics in recent years, the Cas13a system shows great potential as a next-generation platform for accurate, portable, and cost-effective detection of viral and bacterial diseases. Furthermore, we address the existing challenges, including reliance upon amplification and off-target effects, and highlight the need for ongoing research to develop amplification-free systems suitable for clinical application.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"709-726"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484955","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":"The RSPO2 gene is associated with bilateral anterior amelia in Chihuahuas.","authors":"Lucie Chevallier, Marin Green, Julia Vo, Karen Vernau, Denis J Marcellin-Little, Vidhya Jagannathan, Tosso Leeb, Danika Bannasch","doi":"10.1007/s00335-025-10123-1","DOIUrl":"10.1007/s00335-025-10123-1","url":null,"abstract":"<p><p>Bilateral anterior amelia (BAA) is the congenital absence of thoracic limbs and has been reported in the Chihuahua as an autosomal recessive disorder. In some cases, the digits of the pelvic limbs can be variably affected, but otherwise, the pelvic limbs are generally spared. A GWAS performed with nine BAA affected Chihuahuas identified a significant association on chromosome 13, and homozygosity mapping delineated a 2.1 Mb chromosomal region containing the RSPO2 gene. Loss of function variants of RSPO2 in humans and cattle has been associated with the absence of all limbs. Six affected Chihuahuas were whole genome sequenced (WGS) and aligned to the CanFam4 assembly. SNVs, small indels, and structural variants within the critical interval that fitted a recessive model were investigated. Three SNVs (NC_049234.1:g.8891861C > T; NC_049234.1:g.8974204C > T and NC_049234.1:g.9789424G > A) were homozygous in five cases and absent from 3,418 genetically diverse control genome sequences, except for one Small Poodle that was heterozygous. One SNV resided in RSPO2's second intron, while the two others were intergenic. The three candidate variants were genotyped in 7 additional cases and 100 control Chihuahuas. Twelve of 13 cases were homozygous for the mutant allele, and one case was heterozygous. Controls were either homozygous for the reference allele (97%) or heterozygous (3%). Our data should facilitate genetic testing of Chihuahuas to prevent the unintentional production of BAA affected dogs. Moreover, the identification of these variants enhances understanding of RSPO2 gene function in limb development.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"746-760"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710595","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}
Mammalian GenomePub Date : 2025-09-01Epub Date: 2025-05-24DOI: 10.1007/s00335-025-10116-0
Yidong Zhu, Juan Zhao, Zihua Li, Yingqun Chen
{"title":"Identification of senescence-related biomarkers for osteoporosis based on microarray analysis, Mendelian randomization, and experimental validation.","authors":"Yidong Zhu, Juan Zhao, Zihua Li, Yingqun Chen","doi":"10.1007/s00335-025-10116-0","DOIUrl":"10.1007/s00335-025-10116-0","url":null,"abstract":"<p><p>Osteoporosis, characterized by decreased bone mineral density, is a common skeletal disorder in the aging population. Cellular senescence is a key factor in the pathophysiology of osteoporosis. This study aimed to identify senescence-related biomarkers and evaluate the functional role in osteoporosis by integrating microarray analysis, Mendelian randomization (MR), and experimental validation. Osteoporosis-related microarray dataset was downloaded from the Gene Expression Omnibus database for differential expression analysis. We integrated summary-level data from genome-wide association studies on osteoporosis with protein quantitative trait loci data to identify genes with causal relationships to osteoporosis. The senescence-related biomarker gene was identified using the SenMayo gene set and evaluated for the predictive performance through receiver operating characteristic (ROC) curve analysis. Functional enrichment analysis was conducted to explore the underlying mechanisms. Validation of gene expression was performed using quantitative real-time PCR in 50 clinical samples from patients with osteoporosis and controls. A total of 33 differentially expressed genes were identified between osteoporosis and control samples. MR analysis revealed 90 genes with causal effects on osteoporosis. Subsequently, CXCL1 was identified as the key senescence-related biomarker gene. ROC curve analysis demonstrated good predictive performance with an area under the curve value of 0.708. Functional enrichment analysis showed a significant association between CXCL1 and immune-related pathways in osteoporosis. The expression of the gene was successfully validated in clinical samples. This study identified and validated CXCL1 as a senescence-related biomarker with causal effects on osteoporosis through a combination of microarray analysis, MR, and experimental validation. These findings offer insights into the molecular mechanisms of osteoporosis and could inform the development of treatment strategies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"903-913"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135989","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}
Mammalian GenomePub Date : 2025-09-01Epub Date: 2025-06-24DOI: 10.1007/s00335-025-10147-7
Ling Niu, Guangyao Hu
{"title":"FOXP2 mediates ZSCAN18 transcriptional activation to inhibit oral squamous cell carcinoma progression by blocking Hedgehog signaling.","authors":"Ling Niu, Guangyao Hu","doi":"10.1007/s00335-025-10147-7","DOIUrl":"10.1007/s00335-025-10147-7","url":null,"abstract":"<p><p>Zinc finger and SCAN domain-containing (ZSCAN) family members have been implicated in cancer progression. This paper was to assess the role of ZSCAN18 in oral squamous cell carcinoma (OSCC). The OSCC datasets were obtained from the GEO database, and the differentially expressed gene ZSCAN18 was screened for the next analysis. ZSCAN18 protein levels in OSCC tissues and cell lines were investigated. ZSCAN18 was manually overexpressed in OSCC cells to analyze cell proliferation, invasion, migration, and stemness. The protein level of GLI1, a marker protein of the Hedgehog pathway, was detected to determine the effect of ZSCAN18 on this signaling pathway. A mouse xenograft tumor model was constructed to observe tumor growth. Rescue experiments were designed to validate the impact of the FOXP2/ZSCAN18 axis on OSCC. ZSCAN18 was lowly expressed in OSCC and predicted poor prognoses. ZSCAN18 overexpression inhibited OSCC progression, tumor cell stemness, and the Hedgehog pathway. FOXP2, an upstream transcription factor of ZSCAN18, transcriptionally activated ZSCAN18. Rescue experiments further confirmed that FOXP2 transcriptionally activated ZSCAN18 and thus inhibited stemness and tumor growth. Collectively, FOXP2 mediates ZSCAN18 transcriptional activation to inhibit OSCC by blocking Hedgehog signaling.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"939-953"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484957","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}
Mammalian GenomePub Date : 2025-08-22DOI: 10.1007/s00335-025-10154-8
Zidong Li, Yingxuan Guo, Shuai Zhu, Aline M Thomas, Shen Li
{"title":"Inflammatory cytokines are associated with stroke and risk factors of cerebrovascular diseases: a Mendelian randomization study.","authors":"Zidong Li, Yingxuan Guo, Shuai Zhu, Aline M Thomas, Shen Li","doi":"10.1007/s00335-025-10154-8","DOIUrl":"https://doi.org/10.1007/s00335-025-10154-8","url":null,"abstract":"<p><p>The relationship of inflammatory cytokines with the subtypes and prognosis of stroke is not fully understood. Mendelian randomization (MR) was used to evaluate the bidirectional relationship of inflammatory cytokines with stroke subtype (both ischemic and hemorrhagic), and functional outcome of ischemic stroke (modified Rankin Scale score), using databases from Genome-wide association studies, the GISCOME study, the UK Biobank, deCODE, and ONTIME. Colocalization analysis was conducted to determine whether cytokines and stroke subtypes had associations with the same single-nucleotide polymorphism (SNP). Meta-analysis of MR was performed to prove the robustness of the causal relationship between cytokines and stroke subtypes. In addition, both two-step MR analysis and multivariate MR were utilized in mediation analysis to ascertain whether inflammatory cytokines affected stroke subtypes through their regulation of risk factors of cerebrovascular diseases. MR revealed that the genetic prediction of circulating fibroblast growth factor 5 (FGF5) was associated with an increased risk of ischemic stroke and intracranial hemorrhage, but not with the functional outcome of ischemic stroke. Colocalization analysis demonstrated that the association of FGF5 with ischemic stroke and intracranial hemorrhage was driven by the same SNPs. Meta-analyses supported the causal relationship of FGF5 with ischemic stroke and intracranial hemorrhage. Mediation analyses revealed that both essential hypertension and atrial fibrillation mediate the increased risk of ischemic stroke and intracranial hemorrhage due to FGF5. Inflammatory cytokines are associated with stroke and risk factors of cerebrovascular diseases. A high level of circulating fibroblast growth factor 5 is a potential risk factor for stroke.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959429","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":"Genome-wide selective sweep analysis in high-altitude Changthangi goats reveals candidate genes for pashmina fiber production.","authors":"Ram Parsad, Sonika Ahlawat, Mahanthi Vasu, Pooja Chhabra, Upasna Sharma, Reena Arora, Rekha Sharma","doi":"10.1007/s00335-025-10155-7","DOIUrl":"https://doi.org/10.1007/s00335-025-10155-7","url":null,"abstract":"<p><p>Domestic goats (Capra hircus) are vital to global agriculture, with over one billion animals supporting smallholder farmers worldwide. Among goat breeds, the Changthangi goat, native to the trans-Himalayan region of Ladakh, produces pashmina, one of the finest natural fibers (12-16 μm diameter), renowned for its softness and insulation. This study presents the first comprehensive whole-genome comparative analysis between high-altitude pashmina-producing Changthangi goats and lowland Jamunapari goats to elucidate the genetic basis of superior fiber traits. Genome-wide selection signature analyses, including Tajima's D, nucleotide diversity (π), CLR, iHS, F<sub>ST</sub>, and XP-EHH, revealed 2,113 and 839 candidate genes under intra- and inter-population selection, respectively. We identified several candidate genes under selection in Changthangi goats, including those regulating keratinocyte differentiation (BMP2, SMAD3, WNT9B), extracellular matrix organization (COL1A2, ITGA4), and metabolic adaptation (ADCY4, RPS6KB1). Functional annotation and pathway enrichment using DAVID and KEGG databases highlighted key pathways such as Wnt, BMP/TGF-β, Hedgehog, Rap1, PI3K-Akt, and ECM-receptor interaction, which regulate hair follicle morphogenesis, and fiber structure. Gene interaction networks highlighted hub genes (FGF5, SMAD7, COL1A2) critical for fiber traits. Our findings provide novel insights into the genomic signatures underlying elite pashmina production, offering targets for marker-assisted breeding to enhance fiber yield and fineness.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855730","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":"Mapping copy number variable regions correlated with reproduction and production traits in Karan Fries cattle mammalian genomics.","authors":"Oshin Togla, Shivam Bhardwaj, Sagar Kadyan, Yaser Mushtaq Wani, Sabyasachi Mukherjee, Anupama Mukherjee","doi":"10.1007/s00335-025-10152-w","DOIUrl":"https://doi.org/10.1007/s00335-025-10152-w","url":null,"abstract":"<p><p>Copy Number Variants (CNVs) are the structural variations influencing more nucleotides when compared to other types of variations, having a greater impact on the regulation of gene expression, dosage of a gene, altering the coding sequences, all of which might lead to phenotypic variations. Research in the areas of the characterizing CNVs, their discovery and genesis, and their functional effects is in infancy particularly in Indian cattle breeds. We hypothesized that due to the intensive selection for production traits carried out for a premium milch crossbred cattle Karan-fries, they might be characterized by unique CNVs. In order to discover and characterize the genome-wide CNVs and CNV Regions (CNVRs) using HD SNP genotypic array, the current study was carried out on 44 Karan-Fries Cattle. To take use of the complementing advantages of the various methodologies, three distinct approaches (PennCNV, QuantiSNP, and CNVPartition) to identify CNVs were chosen. The techniques mentioned above revealed 2989, 4088, 2316 CNVs, and 980, 1526 917 CNVRegions respectively. The study failed to find a consistent pattern for the number and size of CNV (either overestimation or underestimate by different algorithms). PennCNV algorithm results could be considered to be more accurate than others as there was higher overlapping of PennCNV results by other algorithms. BTA5, BTA12, and BTA17 were significantly enriched for CNVs. QTLs for milk beta-lactoglobulin percentage and interval from estrus to calving were considerably enriched. Using combination of various approaches, the entire CNVR map for Karan-Fries Cattle was developed. This map could be used as a guide for other native breeds and crossbreds.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855731","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}
Mammalian GenomePub Date : 2025-08-04DOI: 10.1007/s00335-025-10153-9
Milena A F Campos, Hinayah Rojas de Oliveira, Gregorio M F de Camargo, Henrique A Mulim, Diercles Francisco Cardoso, Raphael Bermal Costa
{"title":"Beyond black and white: dissecting the genetic basis of skin depigmentation in Nellore cattle.","authors":"Milena A F Campos, Hinayah Rojas de Oliveira, Gregorio M F de Camargo, Henrique A Mulim, Diercles Francisco Cardoso, Raphael Bermal Costa","doi":"10.1007/s00335-025-10153-9","DOIUrl":"https://doi.org/10.1007/s00335-025-10153-9","url":null,"abstract":"<p><p>Depigmentation defects in cattle are characterized by the absence of pigment in specific skin regions, increasing susceptibility to health issues and often leading to early culling. In Nellore cattle, depigmentation is primarily observed at the tail tip, mucous membranes, and as small patches across the body. This study aimed to estimate genetic parameters and perform a genome-wide association study (GWAS) for depigmentation in Nellore cattle. Data were sourced from the DeltaGen® breeding program, provided by Gensys®. Phenotypic records included 182,964 Nellore cattle, with a 6.8% incidence of depigmentation. Of these, 28,655 genotyped animals and 385,079 SNPs were available for the analysis. The ultra-fast generalized linear mixed model for binary traits (fastGWA-GLMM) was used for the GWAS, while variance components were estimated using a Bayesian threshold model and single-step methodology. The heritability of depigmentation was estimated at 0.12 on the observed scale and 0.54 on the liability scale. The GWAS identified 1,011 significant SNPs (p < 0.05 after Bonferroni correction) associated with depigmentation defects, located across chromosomes BTA6, BTA12, and BTA22. However, after performing a conditional GWAS to account for the top signal on BTA22, the original signal in the MITF region was no longer detected. In total, 234 genes were identified near the associated SNPs, including 129 protein-coding genes. Functional enrichment highlighted MITF, KIT and EDNRB as biologically relevant candidate genes. The gene ontology analysis highlighted biological processes related to melanogenesis, pigmentation, and hypopigmentation phenotypes, while the QTL enrichment analysis identified significant associations on BTA6 and BTA22. These findings improve our understanding of the genetic basis of depigmentation in Nellore cattle and may contribute to future selection strategies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784635","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}
Mammalian GenomePub Date : 2025-07-10DOI: 10.1007/s00335-025-10150-y
Danielle M Adams, Murray J Cairns
{"title":"Utilising genomic association data for causal inference in anorexia nervosa.","authors":"Danielle M Adams, Murray J Cairns","doi":"10.1007/s00335-025-10150-y","DOIUrl":"https://doi.org/10.1007/s00335-025-10150-y","url":null,"abstract":"<p><p>Anorexia nervosa (AN) is a prevalent psychiatric disorder with high rates of mortality and limited treatment options. AN is a complex disorder, for which common variation contributes to disorder risk. To dissect the genetic architecture of AN, a variety of statistical methods can be applied. Many of these utilise genome-wide association study (GWAS) datasets to investigate biological mechanisms within disease progression in addition to broader associations between complex traits. GWAS for AN have revealed important biological insights, however, these have not translated into new pharmacotherapies. Here, we review the application of statistical methods that use GWAS, to investigate the relationship between genetic variation, biochemical compounds and complex traits to identify potential relationships which could advance our understanding of disease biology. We discuss genetic variant association data for AN, the application of gene-based and complex trait level correlation methods and approaches for establishing evidence of causality between complex traits and AN. These methods all contribute to the growing literature regarding the genetic influences of AN risk and demonstrate that statistical analysis utilising genetic data is a valuable tool to progress our understanding of this disease.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608731","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}