scholarly journals The Novel ASIC2 Locus Is Associated with Severe Gingival Inflammation

2016 ◽  
Vol 1 (2) ◽  
pp. 163-170 ◽  
Author(s):  
S. Zhang ◽  
K. Divaris ◽  
K. Moss ◽  
N. Yu ◽  
S. Barros ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Periodontal Disease ◽  
Genome Wide Association Study ◽  
Statistical Significance ◽  
Genetic Regulation ◽  
Therapeutic Interventions ◽  
Chromosome 17 ◽  
Gingival Inflammation ◽  
Genome Wide ◽  
A Genome

An increasing body of evidence suggests a significant genetic regulation of inflammatory response mechanisms; however, little is known regarding the genetic determinants of severe gingival inflammation (GI). We conducted a genome-wide association study of severe GI among 4,077 European American adults, participants in the Dental Atherosclerosis Risk in Communities cohort. The severe GI trait was defined dichotomously with the 90th percentile of gingival index ≥2 extent score. Genotyping was performed with the Affymetrix 6.0 array platform, and an imputed set of 2.5 million markers, based on HapMap Phase II CEU build 36, was interrogated. Genetic models were based on logistic regression and controlled for ancestry (10 principal components), sex, age, and examination center. One locus on chromosome 17 met genome-wide statistical significance criteria—lead single-nucleotide polymorphism: rs11652874 (minor allele frequency = 0.06, intronic to ASIC2 [acid-sensing ionic channel 2, formerly named ACCN1]; odds ratio = 2.1, 95% confidence interval = 1.6 to 2.7, P = 3.9 × 10-8). This association persisted among subjects with severe periodontitis and was robust to adjustment for microbial plaque index. Moreover, the minor (G) allele was associated with higher levels of severe GI in stratified analyses among subsets of participants with high load of either “red” or “orange” complex pathogens, although this association was not statistically significant. While these results will require replication in independent samples and confirmation by mechanistic studies, this locus appears as a promising candidate for severe GI. Our findings suggest that genetic variation in ASIC2 is significantly associated with severe GI and that the association is plaque independent. Knowledge Transfer Statement: Persistent gingival inflammation reflected by bleeding usually precedes ongoing attachment loss or periodontal disease progression. Our findings suggest that genetic variation in ASIC2 that is associated with severe gingival inflammation might be used as a genetic marker to identify people at higher risk for periodontal disease. Ongoing studies to uncover the mechanistic link between ASIC2 and gingival inflammation could lead to novel therapeutic interventions.

scholarly journals Genetic Variation in PADI6-PADI4 on 1p36.13 Is Associated with Common Forms of Human Generalized Epilepsy

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1441
Author(s):  
Russell J. Buono ◽  
Jonathan P. Bradfield ◽  
Zhi Wei ◽  
Michael R. Sperling ◽  
Dennis J. Dlugos ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Genome Wide Association Study ◽  
Focal Epilepsy ◽  
Statistical Significance ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Control Of Gene Expression ◽  
Genome Wide ◽  
A Genome ◽  
Generalized Epilepsy

We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance (p ≤ 5 × 10−8) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the PADI6-PADI4 genes that reach genome-wide significance and are associated with disease when comparing GE cases alone to controls. PADI genes encode enzymes that deiminate arginine to citrulline in molecular pathways related to epigenetic regulation of histones and autoantibody formation. Although epilepsy genetics and treatment are focused strongly on ion channel and neurotransmitter mechanisms, these results suggest that epigenetic control of gene expression and the formation of autoantibodies may also play roles in epileptogenesis.

scholarly journals Genetic variation associated with chromosomal aberration frequency: A genome-wide association study

2018 ◽  
Vol 60 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Yasmeen Niazi ◽  
Hauke Thomsen ◽  
Bozena Smolkova ◽  
Ludmila Vodickova ◽  
Sona Vodenkova ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Association Study ◽  
Chromosomal Aberration ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Aberration Frequency ◽  
Genome Wide ◽  
A Genome

scholarly journals Genetics of Germination and Seedling Traits under Drought Stress in a MAGIC Population of Maize

Plants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1786
Author(s):  
Soumeya Rida ◽  
Oula Maafi ◽  
Ana López-Malvar ◽  
Pedro Revilla ◽  
Meriem Riache ◽  
...  
Keyword(s):  
Drought Tolerance ◽  
Genome Wide Association Study ◽  
Genetic Regulation ◽  
Breeding Programs ◽  
Seedling Traits ◽  
Genome Wide ◽  
A Genome ◽  
Positive Correlations ◽  
Genomic Regions ◽  
Magic Population

Drought is one of the most detrimental abiotic stresses hampering seed germination, development, and productivity. Maize is more sensitive to drought than other cereals, especially at seedling stage. Our objective was to study genetic regulation of drought tolerance at germination and during seedling growth in maize. We evaluated 420 RIL with their parents from a multi-parent advanced generation inter-cross (MAGIC) population with PEG-induced drought at germination and seedling establishment. A genome-wide association study (GWAS) was carried out to identify genomic regions associated with drought tolerance. GWAS identified 28 and 16 SNPs significantly associated with germination and seedling traits under stress and well-watered conditions, respectively. Among the SNPs detected, two SNPs had significant associations with several traits with high positive correlations, suggesting a pleiotropic genetic control. Other SNPs were located in regions that harbored major QTLs in previous studies, and co-located with QTLs for cold tolerance previously published for this MAGIC population. The genomic regions comprised several candidate genes related to stresses and plant development. These included numerous drought-responsive genes and transcription factors implicated in germination, seedling traits, and drought tolerance. The current analyses provide information and tools for subsequent studies and breeding programs for improving drought tolerance.

A GENOME-WIDE ASSOCIATION STUDY IN PROGRESSIVE SUPRANUCLEAR PALSY

2015 ◽  
Vol 86 (11) ◽  
pp. e4.68-e4
Author(s):  
Zhongbo Chen ◽  
Aleksey Shatunov ◽  
Gilbert Bensimon ◽  
Christine Payan ◽  
Albert Ludolph ◽  
...  
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Chromosome 17 ◽  
Gene Variants ◽  
Genome Wide ◽  
Mapt Gene ◽  
Common Genetic Variants ◽  
A Genome

BackgroundProgressive supranuclear palsy (PSP) is a debilitating Parkinsonian movement disorder characterised by tau protein burden. We aimed to identify common genetic variants influencing PSP susceptibility through a genome-wide association analysis (GWAS) of a multi-centre European study, Neuroprotection and Natural History in Parkinson's Plus Syndromes (NNIPPS), recruiting clinically well-characterised patients. We combined this with a meta-analysis of previously-identified gene variants.MethodsWe genotyped 275,684 single nucleotide polymorphisms using Illumina microarrays in 212 PSP cases from the UK, Germany and France, and compared these with 4,707 matched controls. GWAS was performed using PLINK. Meta-analysis was performed with METAL. Genome-wide significance was defined as p<5×10^–8.ResultsWe observed multiple associations on chromosome 17 within or close to the MAPT gene, a well-established risk locus for PSP, confirming the sample and method validity. Of nine other previously reported associations, meta-analysis only confirmed that the MOBP variation (rs1768208) modified PSP risk (p=3.29×10^–13).ConclusionIn the GWAS and meta-analysis, we found the chromosome 17 inversion region to be associated with PSP susceptibility. Furthermore, we have shown that MOBP can modify the risk of PSP, possibly through influencing oligodendrocyte tau inclusions. These identified gene variants provide novel insights into the underlying genetics of sporadic PSP.

scholarly journals A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses

BMC Genomics ◽  
2014 ◽  
Vol 15 (1) ◽  
pp. 147 ◽  
Author(s):  
Sarah C Blott ◽  
June E Swinburne ◽  
Charlene Sibbons ◽  
Laura Y Fox-Clipsham ◽  
Maud Helwegen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Fracture Risk ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Thoroughbred Racehorses ◽  
Genome Wide ◽  
A Genome

scholarly journals Elucidating the genetic architecture underlying IGF1 levels and its impact on genomic instability and cancer risk

2021 ◽  
Vol 6 ◽  
pp. 20
Author(s):  
Stasa Stankovic ◽  
Felix R. Day ◽  
Yajie Zhao ◽  
Claudia Langenberg ◽  
Nicholas J. Wareham ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Genome Wide Association Study ◽  
Genetic Regulation ◽  
Epidemiological Studies ◽  
European Ancestry ◽  
Reverse Causality ◽  
Lung Cancers ◽  
Genome Wide ◽  
A Genome ◽  
The Uk

Background: Insulin-like growth factor-1 (IGF1) has been implicated in mitogenic and anti-apoptotic mechanisms that promote susceptibility to cancer development and growth. Previous epidemiological studies have described phenotypic associations between higher circulating levels of IGF1 in adults with higher risks for breast, prostate, ovarian, colorectal, melanoma and lung cancers. However, such evidence is prone to confounding and reverse causality. Furthermore, it is unclear whether IGF1 promotes only the survival and proliferation of cancerous cells, or also the malignant transformation of healthy cells. Methods: We perform a genome-wide association study in 428,525 white European ancestry individuals in the UK Biobank study (UKBB) and identify 831 independent genetic determinants of circulating IGF1 levels, double the number previously reported. Results: Collectively these signals explain ~7.5% of the variance in circulating IGF1 levels in EPIC-Norfolk, with individuals in the highest 10% of genetic risk exhibiting ~1 SD higher levels than those in the lowest 10%. Using a Mendelian randomization approach, we demonstrate that genetically higher circulating IGF1 levels are associated with greater likelihood of mosaic loss of chromosome Y in leukocytes in men in UKBB (OR per +1 SD = 1.038 (95% CI: 1.010-1.067), P=0.008) and 23andMe, Inc. (P=6.8×10-05), a biomarker of genomic instability involved in early tumorigenesis. Genetically higher IGF1 is also associated with higher risks for colorectal (OR = 1.126 (1.048-1.210), P=1.3×10-03) and breast cancer (OR= 1.075 (1.048-1.103), P=3.9×10-08), with similar effects on estrogen positive (ER+) (OR = 1.069 (1.037-1.102), P=2.3×10-05) and estrogen negative (ER-) (OR = 1.074 (1.025-1.125), P=3.9×10-08) subtypes. Conclusions: These findings give an insight into the genetic regulation of circulating IGF1 levels and support a causal role for IGF1 in early tumorigenesis and risks for breast and colorectal cancers.

scholarly journals Mutant Huntingtin Affects Diabetes and Alzheimer’s Markers in Human and Cell Models of Huntington’s Disease

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 962 ◽  
Author(s):  
Gepoliano Chaves ◽  
John Stanley ◽  
Nader Pourmand
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Genome Wide Association Study ◽  
Cell Model ◽  
Statistical Significance ◽  
Mutant Huntingtin ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome ◽  
Reliable Model

A higher incidence of diabetes was observed among family members of individuals affected by Huntington’s Disease with no follow-up studies investigating the genetic nature of the observation. Using a genome-wide association study (GWAS), RNA sequencing (RNA-Seq) analysis and western blotting of Rattus norvegicus and human, we were able to identify that the gene family of sortilin receptors was affected in Huntington’s Disease patients. We observed that less than 5% of SNPs were of statistical significance and that sortilins and HLA/MHC gene expression or SNPs were associated with mutant huntingtin (mHTT). These results suggest that ST14A cells derived from R. norvegicus are a reliable model of HD, since sortilins were identified through analysis of the transcriptome in these cells. These findings help highlight the genes involved in mechanisms targeted by diabetes drugs, such as glucose transporters as well as proteins controlling insulin release related to mHTT. To the best of our knowledge, this is the first GWAS using RNA-Seq data from both ST14A rat HD cell model and human Huntington’s Disease.

Genome-wide association study for buffalo mammary gland morphology

2020 ◽  
Vol 87 (1) ◽  
pp. 27-31
Author(s):  
Jun Li ◽  
Jiajia Liu ◽  
Shenhe Liu ◽  
Giuseppe Campanile ◽  
Angela Salzano ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genetic Regulation ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Chromosome 10 ◽  
Genome Wide ◽  
A Genome ◽  
Mammary Gland Morphology

AbstractThis research communication describes a genome-wide association study for Italian buffalo mammary gland morphology. Three single nucleotide polymorphisms (AX-85117983, AX-8509475 and AX-85117518) were identified to be significantly associated with buffalo anterior teat length, posterior teat length and distance between anterior and posterior teat, respectively. Two significant signals for buffalo mammary gland morphology were observed in two genomic regions on the chromosome 10, and chromosome 20. One of the regions located on the chromosome 10 has the most likely candidate genes ACTC1 and GJD2, both of which have putative roles in the regulation of mammary gland development. This study provides new insights into the genetic variants of buffalo mammary gland morphology and may be beneficial for understanding of the genetic regulation of mammary growth.

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