Annals of Human Genetics最新文献

{"title":"Genomic Structural Equation Modeling Identifies a Shared Inflammatory Genetic Dimension Across Inflammatory Arthritis Phenotypes and Biomarkers.","authors":"Xiaojian Feng, Zhixian Pan, Guoping Liu","doi":"10.1111/ahg.70058","DOIUrl":"https://doi.org/10.1111/ahg.70058","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and gout, shares systemic inflammatory features indexed by C-reactive protein (CRP) and interleukin-6 (IL-6), yet the extent of their common genetic basis remains unclear.</p><p><strong>Aims: </strong>We aimed to delineate the shared genetic architecture across IA phenotypes and inflammatory biomarkers.</p><p><strong>Materials and methods: </strong>We applied genomic structural equation modelling (Genomic SEM) to GWAS summary statistics for RA, PsA, gout, CRP and IL-6, fitted a single common factor, and performed multivariate GWAS followed by fine-mapping, transcriptome-wide association, gene-based analysis, pathway enrichment, and cell-type and spatial mapping.</p><p><strong>Results: </strong>A single common factor was fitted (CFI = 0.990, SRMR = 0.045). The multivariate GWAS identified 56 genome-wide significant SNPs across 10 independent lead loci, including one novel signal. Fine-mapping prioritized high-confidence variants near PTPN22, the CRP gene cluster and a urate-associated locus. Gene-level analyses converged on DCLRE1B, PTPN22, IL6R, NLRP3 and HNF1A, with pathway enrichment implicating inflammasome assembly and metabolic-inflammatory overlap. Cell-type enrichment highlighted myeloid populations, and spatial mapping localized signals to lung, kidney, mucosal epithelium and gastrointestinal tissues.</p><p><strong>Discussion: </strong>These results delineate a shared inflammatory genetic dimension across IA phenotypes and biomarkers, anchored in immune, inflammasome, cytokine-receptor and metabolic pathways.</p><p><strong>Conclusion: </strong>Together, these findings provide a valuable framework for prioritizing candidate genes and cellular contexts for future investigation.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954769","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":"Genetically Proxied Leukocyte Telomere Length and Epigenetic Age Acceleration in Relation to Healthspan: A Mendelian Randomization Study.","authors":"Bowen Feng, Robert Yang, Gabriella R Wang, Qiu Hu, Chuntao Zhao","doi":"10.1111/ahg.70057","DOIUrl":"https://doi.org/10.1111/ahg.70057","url":null,"abstract":"<p><strong>Background: </strong>Leukocyte telomere length (LTL) and epigenetic age acceleration (EAA) are widely studied biomarkers of biological aging, but their potential roles in healthspan remain unclear. We evaluated whether genetically proxied LTL and EAA show evidence of potential effects on healthspan.</p><p><strong>Methods: </strong>We conducted a two-sample Mendelian randomization study. Genetic instruments for LTL and four EAA biomarkers were obtained from published genome-wide association studies, including up to 472,174 individuals for LTL and approximately 35,000 individuals for each EAA biomarker. Summary statistics for healthspan, defined as age at first diagnosis of any of eight major chronic conditions or death, were derived from 300,447 unrelated European-ancestry participants in the UK Biobank. We used inverse-variance-weighted (IVW) models for the main analysis, with complementary MR estimators and sensitivity analyses to evaluate consistency, pleiotropy, instrument heterogeneity, and robustness.</p><p><strong>Results: </strong>Genetically proxied longer LTL was associated with extended healthspan (IVW β = 0.106; 95% CI: 0.054-0.158; p = 6.9 × 10^-5). The association was robust across multiple sensitivity analyses. In contrast, the four genetically proxied EAA biomarkers did not show consistent MR evidence of an association with healthspan.</p><p><strong>Conclusions: </strong>These findings provide genetic evidence consistent with a potential role of LTL in healthspan, while providing little support for comparable associations involving the genetically proxied components of the evaluated EAA biomarkers. The findings do not exclude potential associations with environmentally or physiologically acquired EAA.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918295","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":"Decoding the Genetic and Phenotypic Spectrum of MT-TI Mitochondrial Diseases.","authors":"Enchi Yuan, Ning Zhang, Haoyu He, Tao Zhang, Enze Chen, Qidi Zhang, Dongmei Ji","doi":"10.1111/ahg.70056","DOIUrl":"https://doi.org/10.1111/ahg.70056","url":null,"abstract":"<p><strong>Background: </strong>Variants in the MT-TI gene, which encodes mitochondrial transfer RNA for isoleucine, have been associated with neuromuscular, cardiac, auditory, renal, and metabolic disorders, but their clinical interpretation remains difficult.</p><p><strong>Objective: </strong>To integrate clinical, familial, heteroplasmy, and functional evidence across the reported MT-TI variant spectrum and clarify its implications for variant interpretation and diagnosis.</p><p><strong>Methods: </strong>We conducted a narrative review of reported MT-TI variants, with detailed comparison of seven representative variants and synthesis of phenotypic, familial, tissue-specific heteroplasmy, and functional findings.</p><p><strong>Results: </strong>Evidence was derived mainly from case reports and small pedigrees. Heteroplasmy differed markedly among blood, skeletal muscle, and myocardium, indicating that blood may not represent variant loads in energy-demanding tissues. Reported values generally reflected the lowest observed levels in affected individuals or family-specific boundaries rather than validated pathogenic cutoffs. Functional findings support a staged mechanism involving disturbed transfer RNA processing, structure, stability, or aminoacylation, followed by impaired mitochondrial protein synthesis and respiratory-chain dysfunction. Integrated mechanistic support was limited to a few variants, including m.4295A>G; evidence for most variants remained incomplete or indirect.</p><p><strong>Conclusion: </strong>Diagnosis requires tissue-informed heteroplasmy assessment integrated with phenotype, maternal family history, and functional evidence. Current treatment is supportive, and proposed reproductive and molecular strategies lack MT-TI-specific clinical-trial evidence.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863466","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":"Evidence of a Protective Effect of Metformin on Abdominal Aortic Aneurysm Risk: Insights From an Observational Study and Mendelian Randomisation Analysis Using Putative Metformin Targets","authors":"Katie Louise Saxby,&nbsp;Svetlana Stoma,&nbsp;Frank Dudbridge,&nbsp;Nilesh J. Samani,&nbsp;Matthew J. Bown,&nbsp;Christopher P. Nelson","doi":"10.1111/ahg.70049","DOIUrl":"10.1111/ahg.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>There is no proven treatment to prevent the growth or rupture of abdominal aortic aneurysm (AAA). As an aneurysm enlarges over time, the risk of fatal aortic rupture increases. Metformin, a drug usually prescribed to treat Type 2 diabetes, has previously been associated with reduced AAA risk in observational studies. Our aim was to assess whether there was a causal association between metformin treatment and AAA using Mendelian randomisation (MR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Logistic regression analysis was conducted in UK Biobank with 2972 AAA cases and 89,160 propensity-matched controls. In addition, two-sample MR analysis was performed, using a genetic proxy for metformin consisting of variants associated with both gene expression of seven metformin drug targets and decreased glycated haemoglobin (HbA1c) levels. Effect sizes for HbA1c were obtained from within UK Biobank, and for AAA risk from AAAgen, a multi-ancestry meta-GWAS analysis of 39,221 cases and 1,086,107 controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found evidence of a protective association between self-reported metformin treatment and reduced AAA risk in the observational analysis, OR 0.49 (95% CI: 0.41–0.59, <i>p</i> = 1.5 × 10⁻¹⁴). MR results support this finding, with an estimated decrease in AAA risk of 43%, OR = 0.57 (95% CI: 0.38–0.88, <i>p</i> = 0.010) per one standard deviation (sd) decrease in HbA1c via metformin gene targets, equivalent to the effect of a prescribed dose of metformin. This effect is specific to metformin target genes and was not seen using a general untargeted instrument.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our observational study found evidence that metformin use reduces the risk of developing AAA. The MR results support this finding, providing evidence that the association may be causal. Clinical trials are warranted to assess the efficacy of metformin to reduce the risk of aneurysm growth and rupture in people with AAA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 5","pages":"294-302"},"PeriodicalIF":1.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560699","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}

{"title":"Utility of Urine-Derived Cells for Characterizing Aberrant Splicing Caused by a Novel Deep Intronic L1CAM Variant","authors":"Takuma Harasaki,&nbsp;Sachiko Miyamoto,&nbsp;Takahiro Yonekawa,&nbsp;Masaharu Isogai,&nbsp;Mitsuhiro Kato,&nbsp;Mitsuko Nakashima,&nbsp;Hirotomo Saitsu","doi":"10.1111/ahg.70046","DOIUrl":"10.1111/ahg.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pathogenic variants in <i>L1CAM</i>, located at Xq28, cause a spectrum of neurodevelopmental disorders of varying severity, including congenital hydrocephalus, MASA syndrome, agenesis of the corpus callosum, and intellectual disability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>Exome sequencing (ES) and RNA studies using urine‑derived cells were performed in the younger sibling with agenesis of the corpus callosum, ventriculomegaly, and hearing impairment. A minigene assay was performed to quantitively evaluate the splicing impact of the <i>L1CAM</i> variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified a deep intronic <i>L1CAM</i> variant (NM_001278116.2:c.1124-24T&gt;G) in Intron 10, for which SpliceAI predicts creation of a cryptic acceptor site (score 0.99) via introduction of an AG dinucleotide. The same <i>L1CAM</i> variant was also detected in the older affected brother. RNA studies using of urine‑derived cells UDCs demonstrated retention of a 23‑bp intronic segment in the transcripts, consistent with nonsense‑mediated decay (NMD). Specifically, TA‑cloning of reverse transcription PCR products detected the mutant allele in 2% of colonies, and RNA‑seq recovered the aberrant junction in only 5 of 18 reads. A minigene assay corroborated the mechanism, yielding a variant-specific larger product corresponding to the 23‑bp retained sequence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This report broadens the molecular spectrum of intronic <i>L1CAM</i> variants and underscores the practical value of non‑invasive, UDC-based RNA testing in combination with complementary minigene assays for interpreting deep intronic variants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 5","pages":"278-282"},"PeriodicalIF":1.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395768","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":"Response to Letter on “Downregulation of EPAS1 and EGLN1 mRNA Expression Associated With High-Altitude Adaptive Genetic Variants in Sherpa Highlanders”","authors":"Yunden Droma,&nbsp;Fengming Yue,&nbsp;Masao Ota,&nbsp;Nobumitsu Kobayashi,&nbsp;Yoshiaki Kitaguchi,&nbsp;Masayuki Hanaoka","doi":"10.1111/ahg.70051","DOIUrl":"10.1111/ahg.70051","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 5","pages":"314-315"},"PeriodicalIF":1.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148598087","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":"FIGLA Novel Variant c.385-9G>A Affects RNA Splicing in a Minigene Assay","authors":"Ying Zhang,&nbsp;Jing Hu,&nbsp;Lingyan Ren,&nbsp;Fangfang Li,&nbsp;Cheng Zhang,&nbsp;Juan Liu,&nbsp;Guiqin You,&nbsp;Yurong Feng,&nbsp;Shengwen Huang","doi":"10.1111/ahg.70043","DOIUrl":"10.1111/ahg.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to screen for genetic variants associated with premature ovarian insufficiency (POI) in a Chinese Miao pedigree.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The proband underwent whole exome sequencing (WES), and the extracted data were subjected to bioinformatics analysis using the Rare Disease Data Center (RDDC) splicing tool to identify potential genetic causes in the lineage. Sanger sequencing was employed to confirm the variants in the family, and minigene assays were used to analyze how the <i>FIGLA</i> variant affects pre-mRNA splicing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A novel heterozygous intronic and POI-associated variant in the <i>FIGLA</i> gene (c.385-9G&gt;A) was identified. Splice prediction analysis showed that this variant may disrupt splicing patterns. This result was supported by the outcome of minigene assays, which revealed that the variant led to aberrant splicing of <i>FIGLA</i> introns. As a result, retention of a 7-bp intronic sequence from intron 2 was found in the mature mRNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The <i>FIGLA</i> variant (c.385-9G&gt;A) disrupts mRNA splicing in cells and may contribute to POI in this pedigree. Therefore, our results expand the variant spectrum of the <i>FIGLA</i> gene, provide valuable insights into the pathogenesis of POI for genetic counseling, and may assist clinicians in the early diagnosis of women with infertility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 5","pages":"269-277"},"PeriodicalIF":1.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306630","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":"Distribution of HLA-DRB1 Alleles and Genotypes With Respect to Plasma Anti-SARS-CoV-2 IgG Titres Among COVID-19-Vaccinated Bangladeshi Adults","authors":"Piyash Bhattacharjee,&nbsp;Anika Tahsin,&nbsp;Abdullah Al Saba,&nbsp;Maisha Adiba,&nbsp;Tahirah Yasmin,&nbsp;Akio Ebihara,&nbsp;A. H. M. Nurun Nabi","doi":"10.1111/ahg.70047","DOIUrl":"10.1111/ahg.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Interindividual variations in vaccine-induced immunological responses are well-observed across different populations. This may underlie the highly polymorphic HLA molecules directly involved in antigen presentation to CD4⁺ T cells, leading to the generation of adaptive immunity. With the highest diversity among HLA molecules, HLA-DRB1 alleles and/or genotypes are often hypothesised to be associated with humoral and cellular immune components, as observed in other antiviral vaccines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In this study, we aim to seek an association between HLA-DRB1 alleles and/or genotypes and plasma anti-SARS-CoV-2 (RBD) IgG levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, 98 participants who received two doses of COVID-19 vaccines were subjected to molecular typing of the <i>HLA-DRB1</i> gene in association with the plasma anti-SARS-CoV-2 (RBD) IgG titre.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The seropositive vaccinees had a mean (±SD) anti-SARS-CoV-2 IgG level of 302.89 (±105.64) IU/mL. The most commonly found allele was HLA-DRB1*15 (28.57%), while other alleles with frequencies above 5% were HLA-DRB1*07, HLA-DRB1*12, HLA-DRB1*10, HLA-DRB1*13, HLA-DRB1*04, and HLA-DRB1*03. The most frequent genotype was HLA-DRB1*07/15 (16.32%) among these participants. Other genotypes with frequencies above 5% were HLA-DRB1*10/15, HLA-DRB1*12/15, HLA-DRB1*07/12, HLA-DRB1*13/15, HLA-DRB1*03/15, HLA-DRB1*04/10, HLA-DRB1*07/10, and HLA-DRB1*07/13. The HLA-DRB1*15 allele was associated with anti-SARS-CoV-2 IgG levels among the high-antibody response (HAR) subset for whom more than 180 days (6 months) elapsed post-vaccination. However, no other alleles or genotypes were found to be directly associated with serological status or plasma anti-SARS-CoV-2 IgG levels among the study participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While this study provides insights into the genotypic and allelic distribution of the HLA-DRB1 gene among the Bangladeshi population, further investigation into allelic haplotypes, including other HLA (Class I and Class II) genes, is warranted to determine inter- and intra-population variability in vaccine-mediated protection against SARS-CoV-2.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 5","pages":"283-293"},"PeriodicalIF":1.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395763","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":"Structural Variations of Alu Elements in the Kuwaiti Population: Laying the Foundations for Forensic Medicine","authors":"Seham S. A. Abumarzouq,&nbsp;Alexander Woodman,&nbsp;Abdel Halim Deifalla","doi":"10.1111/ahg.70050","DOIUrl":"10.1111/ahg.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The genetic structure of the Kuwaiti population using Alu insertion variants has not been previously investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to examine the allele and genotype frequencies of 100 Alu insertion variants in the Kuwaiti population, determine their genetic structure in relation to global populations and evaluate the utility of these markers for inferring geographic ancestry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DNA was extracted from whole blood samples of 500 unrelated native Kuwaiti citizens across all six governorates. One hundred known Alu elements were amplified via PCR and analysed using gel electrophoresis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean frequency of the 100 Alu insertions in Kuwaitis was 0.536, showing closer affinity to Eurasian and Indian populations than to sub-Saharan African populations. Analysis of the six Kuwaiti governorates revealed no genetic substructure, suggesting a single genetic cluster. PCA demonstrated that Kuwaitis cluster with geographically adjacent populations, specifically Bahrainis and southern Iranians. Notably, four Alu elements (<i>HS4.32</i>, <i>Ya5NBC120</i>, <i>Yb8NBC106</i> and <i>Yb8NBC516</i>) were identified as potential markers to distinguish Kuwaitis from other populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings confirm existing global data indicating that the use of Alu elements is a crucial tool for population genetic research, given their unique properties that are generally unavailable for other markers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 5","pages":"303-311"},"PeriodicalIF":1.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590196","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":"Letter on ‘Downregulation of EPAS1 and EGLN1 mRNA Expression Associated With High-Altitude Adaptive Genetic Variants in Sherpa Highlanders’","authors":"Maajid Mohi Ud Din Malik","doi":"10.1111/ahg.70045","DOIUrl":"10.1111/ahg.70045","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 5","pages":"312-313"},"PeriodicalIF":1.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590225","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}