scholarly journals FISSURAS LABIAIS E/OU PALATINAS NÃO SINDRÔMICAS: DETERMINANTES AMBIENTAIS E GENÉTICOS.

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Andréa Do Rego Borges ◽  
Jamile De Oliveira Sá ◽  
Lorena Castro Mariano ◽  
Samário Cintra Maranhão ◽  
Alena Peixoto Medrado ◽  
...  
Keyword(s):  
Critical Analysis ◽  
Cleft Lip ◽  
Developmental Disorder ◽  
Association Studies ◽  
Case Control ◽  
Ethnic Composition ◽  
Genome Wide Association Studies ◽  
Orofacial Clefts ◽  
Genome Wide ◽  
Ethnic Factors

The nonsyndromic cleft lip and/or palate (NSCL/P) is a birth anomaly resulting from fusion defects of craniofacial processes. These changes have varied incidence and are more common in nonsyndromic form. The aim of this paper is conduct a literature review about NSCL/P, emphasizing the genetic aspects. In the critical analysis of the selected articles was founded that several genes and chromosomal regions have been associated with orofacial clefts in Genome Wide Association Studies (GWAS), like the genes IRF6, ABCA4, MAFB and region 8q24. It is a developmental disorder of multifactorial origin, involving environmental and genetic agents. The authors also observed strong interference of ethnic factors, particularly in studies of the case-control type. Some polymorphisms were identified in replicated GWAS studies and associated with cleft in the Brazilian population, like the polymorphism rs987525, rs1530300 and rs560426. When the population is stratified, like in Brazil, the ethnic composition has problably a strong effect on the genetic association with NSCL/P. It is recommended the study of genetic ancestry into research’s associating genetic polymorphisms on orofacial clefts.

scholarly journals Genetic factors influencing risk to orofacial clefts: today’s challenges and tomorrow’s opportunities

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2800 ◽  
Author(s):  
Terri H. Beaty ◽  
Mary L. Marazita ◽  
Elizabeth J. Leslie
Keyword(s):  
Birth Defects ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Familial Aggregation ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Orofacial Clefts ◽  
Craniofacial Malformations ◽  
Genome Wide ◽  
The Right

Orofacial clefts include cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), which combined represent the largest group of craniofacial malformations in humans with an overall prevalence of one per 1,000 live births. Each of these birth defects shows strong familial aggregation, suggesting a major genetic component to their etiology. Genetic studies of orofacial clefts extend back centuries, but it has proven difficult to define any single etiologic mechanism because many genes appear to influence risk. Both linkage and association studies have identified several genes influencing risk, but these differ across families and across populations. Genome-wide association studies have identified almost two dozen different genes achieving genome-wide significance, and there are broad classes of ‘causal genes’ for orofacial clefts: a few genes strongly associated with risk and possibly directly responsible for Mendelian syndromes which include orofacial clefts as a key phenotypic feature of the syndrome, and multiple genes with modest individual effects on risk but capable of disrupting normal craniofacial development under the right circumstances (which may include exposure to environmental risk factors). Genomic sequencing studies are now underway which will no doubt reveal additional genes/regions where variants (sequence and structural) can play a role in controlling risk to orofacial clefts. The real challenge to medicine and public health is twofold: to identify specific genes and other etiologic factors in families with affected members and then to devise effective interventions for these different biological mechanisms controlling risk to complex and heterogeneous birth defects such as orofacial clefts.

scholarly journals Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients

2021 ◽  
Author(s):  
Tiit Nikopensius ◽  
Priit Niibo ◽  
Toomas Haller ◽  
Triin Jagomägi ◽  
Ülle Voog-Oras ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Autoimmune Diseases ◽  
Genetic Risk ◽  
Association Studies ◽  
Control Sample ◽  
Case Control ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients. Methods We performed genome-wide association analyses in an entire JIA case–control sample (All-JIA) and in a case–control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls. Results We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10−6), LTBP1 (P = 9,45 × 10−6), and ELMO1 (P = 1,05 × 10−5). In the oligoarticular JIA analysis, the strongest associations were identified at NFIA (P = 5,05 × 10−6), LTBP1 (P = 9,95 × 10−6), MX1 (P = 1,65 × 10−5), and CD200R1 (P = 2,59 × 10−5). Conclusion This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points• Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition.• Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe.• The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci.• The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.

scholarly journals TAGOOS: genome-wide supervised learning of non-coding loci associated to complex phenotypes

2019 ◽  
Vol 47 (14) ◽  
pp. e79-e79
Author(s):  
Aitor González ◽  
Marie Artufel ◽  
Pascal Rihet
Keyword(s):  
Cleft Lip ◽  
Association Studies ◽  
Area Under The Curve ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Functional Snps ◽  
Functional Regions ◽  
Complex Phenotypes ◽  
Genome Wide ◽  
Intergenic Regions

Abstract Genome-wide association studies (GWAS) associate single nucleotide polymorphisms (SNPs) to complex phenotypes. Most human SNPs fall in non-coding regions and are likely regulatory SNPs, but linkage disequilibrium (LD) blocks make it difficult to distinguish functional SNPs. Therefore, putative functional SNPs are usually annotated with molecular markers of gene regulatory regions and prioritized with dedicated prediction tools. We integrated associated SNPs, LD blocks and regulatory features into a supervised model called TAGOOS (TAG SNP bOOSting) and computed scores genome-wide. The TAGOOS scores enriched and prioritized unseen associated SNPs with an odds ratio of 4.3 and 3.5 and an area under the curve (AUC) of 0.65 and 0.6 for intronic and intergenic regions, respectively. The TAGOOS score was correlated with the maximal significance of associated SNPs and expression quantitative trait loci (eQTLs) and with the number of biological samples annotated for key regulatory features. Analysis of loci and regions associated to cleft lip and human adult height phenotypes recovered known functional loci and predicted new functional loci enriched in transcriptions factors related to the phenotypes. In conclusion, we trained a supervised model based on associated SNPs to prioritize putative functional regions. The TAGOOS scores, annotations and UCSC genome tracks are available here: https://tagoos.readthedocs.io.

scholarly journals Powerful SNP-Set Analysis for Case-Control Genome-wide Association Studies

2010 ◽  
Vol 86 (6) ◽  
pp. 929-942 ◽  
Author(s):  
Michael C. Wu ◽  
Peter Kraft ◽  
Michael P. Epstein ◽  
Deanne M. Taylor ◽  
Stephen J. Chanock ◽  
...  
Keyword(s):  
Association Studies ◽  
Case Control ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide
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