Human Genetics最新文献

{"title":"A genome-wide association study of cognitive impairment in a Chinese cohort of 1,040 individuals.","authors":"Maggie Haitian Wang, Yexian Zhang, Rui Sun, Fudong Li, Tao Zhang, Xue Gu, Jingzhi Lou, Lirong Cao, Shimin Su, Hong Zheng, Caiqi Liu, Marc Ka Chun Chong, William Ka Kei Wu, Jun Yu, Benny Chung-Ying Zee, Junfen Lin","doi":"10.1007/s00439-026-02887-6","DOIUrl":"10.1007/s00439-026-02887-6","url":null,"abstract":"<p><p>While genetic heritability plays a major role in the development of cognitive impairment, most genetic risk factors are identified from studies of European populations. We conducted a genome-wide association study (GWAS) on cognitive impairment in the Chinese population by sequencing 1,040 matched case-control individuals from a longitudinal cohort of Zhejiang Province, China. We detected 19 SNPs clustered in 15 genomic loci reaching suggestive significance (P < 1 × 10^- 5). Eleven of these genomic loci are newly associated with Alzheimer's disease (AD) or cognitive impairment, among which five (GRP39, FAT1, EDIL3, ZNF596, and PDGFD) show nominal evidence of replication in both external GWAS of AD in East-Asian populations and summary statistics of AD in diverse populations. The detected loci are implicated in micronutrient homeostasis including zinc (GPR39), iron (STEAP1), potassium (KCNJ6), and vitamin K (VKORC1L1), cell connections (EVPLL) through cadherin regulations (PCDH18, FAT1), regulating amyloid-beta precursor protein (APP) (EDIL3), formation of amyloid-β (EDEM1) and neurofibrillary tangles (PDGFD, ZNF596), neuronal growth (NEGR1), and phosphatase regulations (SETBP1, TPTE). This study presents a robust GWAS for cognitive impairment in the Chinese population and highlights a promising set of therapeutic targets for neurodegenerative disorder.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interobserver reliability and digital morphometric characterization of constitutional chromosomal heteromorphisms in clinical cytogenetics.","authors":"Omar Casadiego, Jennifer Castro, Aura Mantilla, Thomas Vanegas, Nathaly Ramírez-García, Laura Fernanda Neira Fuentes, Norma Serrano","doi":"10.1007/s00439-026-02886-7","DOIUrl":"https://doi.org/10.1007/s00439-026-02886-7","url":null,"abstract":"<p><p>Constitutional chromosomal heteromorphisms are common cytogenetic variants involving constitutive heterochromatin and acrocentric short-arm structures whose visual identification and classification remain challenging in routine cytogenetic practice. This study evaluated interobserver reliability in the visual classification of constitutional chromosomal heteromorphisms and characterized differences between homologous chromosomes using digital morphometry. A retrospective cross-sectional study included peripheral blood cytogenetic studies performed between 2021 and 2024. Sixty-six cases with previously reported heteromorphisms were included, yielding 73 heteromorphism observations. Four cytogeneticists, blinded to the original classification and clinical information, independently evaluated selected Q-banded metaphases using predefined visual criteria. Interobserver agreement was assessed using Krippendorff's alpha and Gwet's AC1. Digital morphometric analysis was performed in Fiji by measuring the chromosomal region associated with each heteromorphism, defined as the target region (TR), and calculating its absolute size and its ratio to total chromosome size (TR/T). Homologous chromosomes were compared using the Wilcoxon signed-rank test. Overall observed agreement was 70.1%, and complete agreement among the four cytogeneticists was observed in 45.5% of metaphases. Krippendorff's alpha was 0.340 (95% CI 0.276-0.398), and Gwet's AC1 was 0.453 (95% CI 0.380-0.532). Positive specific agreement was higher than negative specific agreement (77.1% vs. 56.9%). Significant morphometric asymmetry was identified in 11.0% of observations using absolute TR measurements and in 15.1% using TR/T. Findings for the acrocentric subgroup were based on only six observations and should be interpreted cautiously. Overall, visual classification showed limited reproducibility, particularly for pericentromeric heterochromatic variants. Digital morphometry provided complementary quantitative descriptors but did not resolve the limitations of classification based on chromosome morphology and should not be used as a confirmatory criterion.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-based association analysis of depression risk among European ancestry Parkinson's disease patients.","authors":"Hanwen Wang, Kimberly Paul, Cynthia Kusters, Christina M Lill, Jin Zhou, Jeff Bronstein, Beate Ritz","doi":"10.1007/s00439-026-02877-8","DOIUrl":"10.1007/s00439-026-02877-8","url":null,"abstract":"<p><p>Depression is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD), yet its genetic basis remains poorly understood. Here, we investigate the genetic contributions to depression in PD by estimating the burden from common as well as low-frequency single nucleotide polymorphisms (SNPs) within genes previously implicated in PD or depression risk among European ancestry PD patients from three population-based studies. Using gene-based association analyses (SKAT, Burden, and SKAT-O) in the PASIDA, PEG, and PPMI studies, we evaluated SNP sets in gene regions previously linked to PD or depression. Among PD-related genes, meta-analysis identified a significant association between KRTCAP2 and self-reported depression diagnosis in PD (SKAT-O p = 4.33 × 10⁻⁵), which remained significant after false discovery rate correction. A higher genetic burden in KRTCAP2 was associated with 20% increased odds of depression (OR = 1.20, 95% CI: 1.04-1.38). TRAF5 and LRRK2 showed marginal associations. Among depression-related genes, SPPL3 and ERBB4 were associated with depression diagnosis history, and FNIP2 was associated with current depressive symptoms. The PD polygenic risk score was not associated with depression in PD, while a higher depression polygenic risk score was significantly associated with increased odds of depression diagnosis in both cohorts and the meta-analysis (OR = 1.26, 95% CI: 1.13-1.40). Our findings highlight immune-related genes such as KRTCAP2 and TRAF5 as potential contributors to depression in PD. Additionally, the depression PRS shows statistically significant association with depression diagnosis in PD, suggesting that a general depression-related genetic liability contributes to this non-motor feature in PD. Together, these results suggest that depression in PD may involve both shared and disease-specific genetic mechanisms, offering new insights into its pathogenesis and potential therapeutic targets.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of familial short stature with or without skeletal dysplasia in a Pakistani cohort reveals founder mutations as well as novel variants.","authors":"Tayyaba Ishaq, Amatul Raqeeb Jawaid, Samina Yasin, Noor Ul Ain, Ambreen Faryal, Memoona Shaukat, Muhammad Noman, Niaz Muhammad, Muddassar Iqbal, Fatema Alzahrani, Anum Shafique, Rimsha Zulfiqar, Ambreen Kanwal, Fowzan S Alkuraya, Elizabeth Wohler, Nara Sobreira, Go Hun Seo, Outi Makitie, Sadaf Naz","doi":"10.1007/s00439-026-02883-w","DOIUrl":"https://doi.org/10.1007/s00439-026-02883-w","url":null,"abstract":"<p><p>Skeletal dysplasias are a diverse group of genetically inherited bone disorders which may manifest with or without short stature. Extreme short stature can also result from different growth hormone deficiencies. Our research aimed to identify the genetic causes of recessively inherited short stature, with or without skeletal abnormalities in Pakistani families. We recruited participants from thirty-eight pedigrees with a history of these disorders. Radiological examinations were performed for a few patients. Some samples were first screened for variants in GHRHR and RMRP by Sanger sequencing. Next, exome sequencing was carried out for selected patients from each family. Exome data were annotated and all were analyzed using Franklin software while some data were also analyzed using the 3billion automated system. Candidate variants were confirmed by segregation analyses in each family. We identified ten novel homozygous variants in AARS2, COL2A1, ERCC6, EVC2, GHR, IHH, MYH3, NPR2, OBSL1 and TG segregating with the phenotypes in ten different families. In-silico analyses predicted these variants to be deleterious to the genes or the encoded proteins. AARS2 variants have not been previously described to cause short stature. Members of the other twenty-five families had variants in nine different genes. A GHRHR founder mutation accounted for short stature without skeletal abnormalities in 12 families. In contrast, significant genetic heterogeneity was observed in the group of families with short stature accompanied by skeletal dysplasia. In conclusion, our study has broadened the genotypic and phenotypic spectrum of multiple genes and the associated diseases with short stature and skeletal dysplasia.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular spectrum of congenital disorders of glycosylation in 80 Egyptian patients.","authors":"Mohamed S Abdel-Hamid, Sherif F Abdel-Ghafar, Mahmoud Y Issa, Walaa ElNaggar, Hasnaa M Elbendary, Karima Rafat, Nagwa Gaboon, Mahmoud M Noureldeen, Ziad N Rezk, Nour Elkhateeb, Laila Selim, Joseph G Gleeson, Maha S Zaki","doi":"10.1007/s00439-026-02881-y","DOIUrl":"10.1007/s00439-026-02881-y","url":null,"abstract":"<p><p>Congenital disorders of glycosylation (CDG) represent a diverse group of inborn errors of metabolism caused by defective glycosylation processes, usually characterized by multiorgan involvement and overlapping clinical symptoms. This study aimed to decipher the clinical and genetic landscape of CDG in Egypt to enumerate the most common CDG types and unveil potentially new candidate genes. The study included 80 patients from 57 families with molecular findings consistent with CDG. Consanguinity was noted in 90% of the families. The most common clinical features were global developmental delay (98%), dysmorphic facies (86%), hypotonia (85%), movement disorders (48%), and seizures (42%). Vision impairment, hepatic, skeletal, and hematological abnormalities were the most frequently encountered systemic manifestations. Structural brain anomalies were commonly observed in our cohort and included thin corpus callosum, cortical atrophy, white matter abnormalities, cerebellar atrophy, and cerebellar vermis hypoplasia. Biallelic variants were identified in 94% of patients, while 6% had variants in X-linked genes. A total of 53 variants were identified in 29 genes, of which 38 (72%) were novel. The most frequent variants were in SRD5A3 (16%), PMM2 (11%), ALG1 (10%), NGLY1 (7.5%), MGAT2 (6%), and ALG11 (5%). We identified two sibs with a homozygous missense variant in CAMLG, which has been recently described in only one case, supporting its role as a new CDG type. Additionally, we described a case with the recently reported UGGT1-CDG and proposed ALG10 as a potentially new CDG gene. Our study highlights the striking phenotypic and genotypic variability associated with CDG and broadens the spectrum of variants and causative genes.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geographic barrier contributed to the diversity of maternal and paternal lineages in New Guinea Island.","authors":"Mariko Isshiki, Augustinus Soemantri, Ryutaro Ohtsuka, Minato Nakazawa, Takafumi Ishida, Jun Ohashi","doi":"10.1007/s00439-026-02869-8","DOIUrl":"10.1007/s00439-026-02869-8","url":null,"abstract":"<p><p>Migration into Sahul is one of the earliest migrations which required open-sea voyages. Two primary routes from Sunda-the northern and southern routes-have been proposed, yet the details of human dispersal into and within Sahul remain unclear. Here, we analyzed mitochondrial DNA (mtDNA) and Non-Recombining Region of the Y chromosome (NRY) sequences of 163 unrelated individuals-80 of whom were newly sequenced in this study-sampled from 12 distinct regions across New Guinea Island and the surrounding islands, in order to reconstruct the demographic history of northern Sahul and to evaluate how cultural and geographic factors have shaped genetic variation. The distribution of mtDNA and Y haplogroups exhibits strong geographic structuring. Austronesian-derived haplogroups are largely restricted to coastal regions, while mtDNA haplogroups N and S, previously observed exclusively in Aboriginal Austronesians, are concentrated in the south. Phylogenetic analyses revealed a distinct west-east split ~ 20-30 kya in mtDNA haplogroup Q and Y haplogroups, suggesting that the present-day residential patterns could be established during this early period. Higher mtDNA haplogroup diversity compared to NRY, along with stronger population stratification in NRY, indicates a predominantly patrilocal social structure, consistent with previous findings. Additionally, elevated nucleotide diversity across multiple haplogroups in the Bird's Head region supports the hypothesis of a northern migration route. Furthermore, we uncovered robust evidence that the Central Range has functioned as a significant geographic barrier influencing genetic variation across the island. Together, these findings highlight the complex demographic history of northern Sahul and a significant effect of non-genetic factors on their genetic diversity.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annual average exposure to ambient air pollution, polygenic risk, and incidence of major chronic diseases: a large-scale prospective cohort study.","authors":"Jing Tian, Sicong Wang, Xinyi Chang, Yi Han","doi":"10.1007/s00439-026-02875-w","DOIUrl":"10.1007/s00439-026-02875-w","url":null,"abstract":"<p><p>Ambient air pollution is a major environmental risk factor for chronic diseases, yet its independent effects, as well as its joint associations and interactions with genetic susceptibility, on multiple chronic conditions remain understudied. This study aims to investigate the association between annual average exposure to multiple air pollutants and five major chronic diseases, while quantifying the role of polygenic risk in these relationships. We included 313,534 participants from the UK Biobank. Land use regression models were used to estimate annual average air pollution concentrations at residential addresses. Chronic diseases (cardiovascular, respiratory, neurodegenerative, hypertension, and diabetes) were identified using ICD-9 and ICD-10 codes. Weighted polygenic risk scores (PRS) were constructed for each disease. Cox proportional hazards models were used to assess associations, and additive interactions were evaluated using RERI and AP. Annual average exposure to PM2.5, PM10, NO2, and NOx was significantly associated with increased chronic disease risk. PM2.5 showed the strongest association (HR = 1.22 per 5 µg/m³, 95% CI: 1.19-1.26). High genetic risk was independently associated with disease incidence (e.g., diabetes: HR = 1.77 per SD increase in PRS). Significant additive interactions were observed between high genetic risk and high PM2.5 exposure for neurodegenerative disease (RERI = 0.14) and diabetes (RERI = 0.21). Participants with both high genetic risk and high pollution exposure had the highest disease burden. Annual average exposure to air pollutants is associated with increased risks of multiple chronic diseases, with effect modification by genetic susceptibility.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of apolipoprotein E gene with risk, cognition, and prognosis of epilepsy.","authors":"Shengyi Liu, Lingjie Fan, Zihua He, Tong Yi, Jiaqi Wang, Junhan Zhao, Josemir W Sander, Dong Zhou, Jinmei Li","doi":"10.1007/s00439-026-02876-9","DOIUrl":"10.1007/s00439-026-02876-9","url":null,"abstract":"<p><p>Previous experimental studies suggested a link between the apolipoprotein E (APOE) gene and epilepsy. However, clinical studies have failed to reach a definitive conclusion on the association. We conducted a cohort study to investigate the clinical correlation between APOE ε4 and epilepsy. This study was based on the UK Biobank. Participants were divided according to the number of APOE ε4 carriers. A Cox proportional hazards model was used to analyse the association between APOE ε4 and the risk of epilepsy, and the association between APOE ε4 and dementia after epilepsy, and the association between APOE ε4 and death. The presence of the APOE ε4 allele was associated with an increased risk of epilepsy, particularly late-onset epilepsy, but the difference in the proportion of APOE ε4 carriers compared with controls in post-stroke epilepsy varied by condition. APOE ε4 carriers were found to have a higher likelihood of dementia following epilepsy onset, with those carrying one copy of the APOE ε4 allele having an approximately 80% higher risk of dementia after epilepsy, and those carrying two copies of the APOE ε4 allele having an approximately 225% higher risk of dementia after epilepsy. APOE ε4 carriers with epilepsy also showed an elevated risk of death, with a trend toward increased risk in those carrying one copy of the APOE ε4 allele and an approximately 39% higher risk of death in those carrying two copies of the APOE ε4 allele. The APOE ε4 allele was associated with an increased risk of epilepsy, particularly late-onset epilepsy among homozygous carriers. Among participants with epilepsy, APOE ε4 carrier status was associated with an increased risk of dementia and premature death, particularly death from neurological causes.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, immunological, and molecular characteristics of severe combined immune deficiency in China.","authors":"Feifan Xiao, Qinhua Zhou, Chenghao Wang, Haili Yao, Jia Hou, Bijun Sun, Wenjing Ying, Xiaoying Hui, Lipin Liu, Liangyan Zou, Luyao Liu, Ying Wang, Xiaowen Qian, Xiaowen Zhai, Bingbing Wu, Wenhao Zhou, Jinqiao Sun, Wenjie Wang, Xiaochuan Wang","doi":"10.1007/s00439-026-02879-6","DOIUrl":"10.1007/s00439-026-02879-6","url":null,"abstract":"<p><p>Severe combined immunodeficiency (SCID) is an inborn error of immunity. The clinical and genetic characteristics of SCID remain poorly characterized in China. This study aimed to analyze the clinical, immunological, and molecular features of the largest cohort of SCID patients from a single center in China. This retrospective study was conducted at the Children's Hospital of Fudan University. Patients diagnosed with SCID between January 2013 and May 2025 were enrolled. A total of 148 patients were included. The mean age at disease onset was 10.7 months, while the mean age at diagnosis was 18.9 months. The most common clinical manifestations included pneumonia (95.3%), diarrhea (52.0%), and hepatomegaly (43.9%). Genetic testing was performed in 134 patients, among whom 121 received a genetic diagnosis, yielding a molecular diagnostic rate of 90.3% (121/134). Variants in 12 distinct genes were identified. The most frequently implicated genes were IL2RG (34.7%), RAG1 (22.3%), RAG2 (9.1%), and LIG4 (8.3%). These four genes accounted for 74.4% of the diagnosed cases. Among the 66 patients who underwent hematopoietic stem cell transplantation, the mortality rate was 36.1% (13/36) in the typical SCID group and 41.4% (12/29) in the atypical group. In conclusion, this study reports the largest cohort of SCID patients in China. Our analysis outlines the clinical, immunological, and genetic spectrum of the disease.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case-control study on IL-8 gene polymorphisms and serum IL-8 levels in patients with age-related macular degeneration in India.","authors":"Anshu Yadav, Jitender Phogat, Manoj Yadav, Aarti Bhardwaj, Vishal Panghal, Supreme Goel, Mamta Verma, Sapna Sharma, Mayank Singh, Rakesh Kumar, Mukesh Tanwar","doi":"10.1007/s00439-026-02874-x","DOIUrl":"10.1007/s00439-026-02874-x","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a leading cause of vision loss, with inflammatory and genetic factors contributing to its development. This study examined the association of IL-8 polymorphisms (rs4073, rs2227306, rs2227543) and serum IL-8 levels in a North Indian AMD cohort. A case-control study involving 160 AMD patients and 100 controls was performed. AMD was confirmed through detailed clinical evaluation and diagnostic imaging. Genomic DNA was extracted and genotyped using PCR followed by Sanger sequencing, and serum IL-8 concentrations were determined by ELISA. Statistical analyses were conducted using SPSS v22.0 and SNPstats. AMD patients exhibited significantly higher serum IL-8 levels than control (p < 0.001). ANCOVA adjusting for age and smoking confirmed elevated IL-8 in AMD (adjusted mean: 63.52 pg/ml vs. 41.23 pg/ml in controls; p < 0.001), with higher levels in wet AMD than dry AMD (67.75 pg/ml vs. 54.32 pg/ml; p = 0.043). The IL-8 rs4073 AA genotype and A allele were more frequent in AMD patients (p = 0.006 and p = 0.011, respectively). Multivariate logistic regression showed strong associations between rs4073 AA genotype and AMD risk under codominant (adjusted OR = 2.68; 95% CI: 1.17-6.15; p = 0.025), recessive (adjusted OR = 2.68; 95% CI: 1.27-5.67; p = 0.0067), and log-additive (adjusted OR = 1.50; 95% CI: 1.02-2.20; p = 0.036) models. No significant associations were observed for rs2227306 or rs2227543. Among all participants, AA carriers had significantly higher serum IL-8 levels than TT and AT genotypes (p = 0.018 and p < 0.001). The IL-8 rs4073 AA genotype and elevated serum IL-8 levels may serve as potential markers for AMD susceptibility in the North Indian population.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}