CXADR polymorphism rs6517774 modifies islet autoimmunity characteristics and exhibits sex disparity DOI Creative Commons
Lucas Nygård, Milla Valta, Antti‐Pekka Laine

et al.

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 2, 2023

Enteroviral infections have been linked to the development of islet autoimmunity (IA) and type 1 diabetes (T1D), coxsackie adenovirus receptor (CXADR) is one ligands used by adenoviruses enteroviruses for cell internalization. Two CXADR single nucleotide polymorphisms (SNPs), rs6517774 rs2824404, were previously associated with an increased susceptibility IA in international TEDDY study (The Environmental Determinants Diabetes Young). This aimed replicate results genotyping 2886 children enrolled Finnish Prediction Prevention (DIPP). In our preliminary analysis SNPs’ allelic distributions, we could not find any association susceptibility. However, a stratified revealed sex disparity, since distribution was different when comparing autoantibody positive females males; difference seen healthy subjects. By using HLA risk groups as covariates, Cox regression survival found that (A/G) SNP lower age at seroconversion (Female*rs6517774-AA; HR = 1.53, p 0.002), while introducing protective effect males. Accordingly, propose alters characteristics modifying sex-dependent manner. light this observation, now joins limited set on SNPs introduce effects initiation.

Language: Английский

FORGEdb: a tool for identifying candidate functional variants and uncovering target genes and mechanisms for complex diseases DOI Creative Commons
Charles E. Breeze, Eric Haugen, María Gutiérrez‐Arcelus

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 2, 2024

The majority of disease-associated variants identified through genome-wide association studies are located outside protein-coding regions. Prioritizing candidate regulatory and gene targets to identify potential biological mechanisms for further functional experiments can be challenging. To address this challenge, we developed FORGEdb ( https://forgedb.cancer.gov/ ; https://forge2.altiusinstitute.org/files/forgedb.html https://doi.org/10.5281/zenodo.10067458 ), a standalone web-based tool that integrates multiple datasets, delivering information on associated elements, transcription factor binding sites, target genes over 37 million variants. scores provide researchers with quantitative assessment the relative importance each variant targeted experiments.

Language: Английский

Citations

16
Exploring the relationship between melanopsin gene variants, sleep, and markers of brain health DOI Creative Commons
Ayeisha Milligan Armstrong, Eleanor K. O’Brien, Tenielle Porter

et al.

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 1, 2025

Abstract INTRODUCTION Melanopsin is a photopigment with roles in mediating sleep and circadian‐related processes, which are often disrupted Alzheimer's disease (AD). also impacts cognition synaptogenesis. This study investigated the associations between melanopsin genetic variants, sleep, markers of brain health. METHODS Linear regression analyses examined relationship single‐nucleotide polymorphisms (SNPs) within gene ( OPN4 ), cortical amyloid beta (Aβ), cognition, volumes, self‐reported traits cognitively unimpaired older adults. Further assessed whether x SNP interactions were associated RESULTS SNPs rs2355009 rs3740334 attention processing speed ventricular volume language, respectively. Furthermore, rs1079610 showed significant association language. DISCUSSION shows variants health, suggests that these interact to exacerbate cognitive effects. Highlights The relationships ) health cross‐sectionally individuals. Variation differences volume. show small–moderate speed. this, volumes language performance, performance.

Language: Английский

Citations

0
Genome-Wide Association Studies: A Powerful Approach for Identifying Genomic Variants for Livestock Breeding and Disease Management DOI
Min‐Jae Jang, Seung-Hoon Lee, Jun‐Mo Kim

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Genome‐Wide Association Analyses of HPV16 and HPV18 Seropositivity Identify Susceptibility Loci for Cervical Cancer DOI Creative Commons

Theresa Beckhaus,

Linda Kachuri, Taishi Nakase

et al.

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Jan. 31, 2025

Infection by high-risk human papillomavirus is known to exacerbate cervical cancer development. The host immune response crucial in disease regression. Large-scale genetic association studies for have identified few susceptibility variants, mainly at the leukocyte antigen locus on chromosome 6. We hypothesized that modifies risk and performed three genome-wide analyses HPV16, HPV18 HPV16/18 seropositivity 7814, 7924, 7924 samples from UK Biobank, followed validation genotyping German Cervigen case-control series of dysplasia. In GWAS analyses, we two loci associated with HPV16 (6p21.32 15q26.2), (5q31.2 14q24.3), one and/or (at 6p21.32). MAGMA gene-based analysis HLA-DQA1 HLA-DQB1 as significant (GWS) genes. genotyping, lead variant 6p21.32, rs9272293 overall (OR = 0.86, p 0.004, 95% CI 0.78-0.95, n 3710) positive invasive 0.73, 0.005, 0.59-0.91, 1431). This was found be a robust eQTL HLA-DRB1, HLA-DQB1-AS1, C4B, HLA-DRB5, HLA-DRB6, HLA-DQB1, HLA-DPB1 epithelial tissue samples. additionally genotyped twenty-four HPV variants below GWS threshold out which eleven were our cohort, suggesting further may determine outcome. Our study identifies novel genomic associate type-specific dysplasia provides evidence candidate genes loci.

Language: Английский

Citations

0
Mapping the landscape of childhood obesity: genomic insights and socioeconomic status in Indian school‐going children DOI

Janaki M. Nair,

Ganesh Chauhan, Gauri Prasad

et al.

Obesity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Objective Childhood obesity (OB) is influenced by complex gene–environmental interaction. While genetics of adult OB have been extensively studied, polygenic childhood in non‐European populations still underexplored. Furthermore, a developing nation such as India, how the environmental component strongly modulated socioeconomic status (SES) shapes genetic susceptibility crucial to understand. Methods A two‐staged genome‐wide association study (GWAS; N = 5673) and an independent exome‐wide (ExWAS; 4963) were performed using generalized linear model assuming additive effect identify common rare variants respectively associated with OB. Rare‐variant burden testing was also performed. We used gene expression profiles regulatory data from public databases explain novel associations. The implications SES potential modifier evaluated. Results GWAS identified associations TCF7L2 , IMMP2L IPMK CDC5L SNTG1 MX1 whereas ExWAS uncovered CNTN4 COQ4 TNFRSF10D FLG‐AS1 BMP3 . Both validated known FTO MC4R rare‐variant highlighted role 101 genes. observed that can modulate inherent Conclusions Our interaction

Language: Английский

Citations

0
TBC1D30 regulates proinsulin and insulin secretion and is the target of a genomic association signal for proinsulin DOI
Victoria A. Parsons, Swarooparani Vadlamudi, Kayleigh M. Voos

et al.

Diabetologia, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

Citations

0
Novel ABCD1 and MTHFSD Variants in Taiwanese Bipolar Disorder: A Genetic Association Study DOI Creative Commons

Yiguang Wang,

Chih-Chung Huang, Ta‐Chuan Yeh

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(3), P. 486 - 486

Published: March 11, 2025

Background and Objectives: In recent years, bipolar disorder (BD), a multifaceted mood marked by severe episodic fluctuations, has been shown to have an impact on disability-adjusted life years (DALYs). The increasing prevalence of BD highlights the need for better diagnostic tools, particularly those involving genetic insights. Genetic association studies can play crucial role in identifying variations linked BD, shedding light its underpinnings potential therapeutic targets. This study aimed identify novel variants associated with Taiwanese Han population elucidate their roles disease pathogenesis. Materials Methods: Genotyping was conducted using Taiwan Precision Medicine Array (TPM Array) 128 patients 26,122 control subjects. Following quality control, 280,177 single nucleotide polymorphisms (SNPs) were analyzed via chi-square tests, linkage disequilibrium (LD) analyses employed examine associations among key SNPs. Results: Eleven SNPs reached significance (p < 10−5), variant rs11156606 ABCD1 gene—implicated fatty acid metabolism—emerging as prominent finding. LD analysis revealed that is strongly rs73640819, located 3′ untranslated region, suggesting regulatory gene expression. Additionally, rs3829533 MTHFSD found be strong missense rs3751800 rs3751801, indicating alterations protein function. Conclusion: These findings enhance understanding within cohort risk-associated support these markers early diagnosis targeted strategies.

Language: Английский

Citations

0
Novel genetic associations with childhood adipocytokines in Indian adolescents DOI

Janaki M. Nair,

Ganesh Chauhan, Gauri Prasad

et al.

Cytokine, Journal Year: 2025, Volume and Issue: 190, P. 156935 - 156935

Published: April 7, 2025

Language: Английский

Citations

0
PPDPF is not a key regulator of human pancreas development DOI Creative Commons
Markus Breunig, Meike Hohwieler,

Jasmin Haderspeck

et al.

PLoS Genetics, Journal Year: 2025, Volume and Issue: 21(4), P. e1011657 - e1011657

Published: April 7, 2025

Given their capability to differentiate into each cell type of the human body, pluripotent stem cells (hPSCs) provide a unique platform for developmental studies. In current study, we employed this system understand role pancreatic progenitor differentiation and proliferation factor (PPDPF), protein that has been little explored so far. While zebrafish orthologue exdpf is essential exocrine pancreas specification, its importance mammalian development not studied yet. We implemented four times CRISPR/Cas9 nicking approach knockout PPDPF in embryonic (hESCs) differentiated KO/KO WT/WT towards lineage. contrast data obtained from zebrafish, very modest effect was observed progenitors vitro , affecting lineage specification upon orthotopic transplantation vivo . The line with finding genetic variants near are associated random glucose levels humans, but 2 diabetes risk, supporting dysregulation gene may only result minor alterations glycaemic balance humans. addition, less organ- specifically expressed higher vertebrates far reported functions appear highly context-dependent.

Language: Английский

Citations

0
Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele DOI Creative Commons
Xinruo Zhang, Jennifer A. Brody, Mariaelisa Graff

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 11, 2025

Language: Английский

Citations

0