Studying the effects of haplotype partitioning methods on the RA-associated genomic results from the North American Rheumatoid Arthritis Consortium (NARAC) dataset

Saad, Mohamed N.; Mabrouk, Mai S.; Eldeib, Ayman M.; Shaker, Olfat G.

doi:10.1016/j.jare.2019.01.006

Cited by 12 publications

(8 citation statements)

References 144 publications

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“…These include CFL2 and SVEP1 and several genes with a suggestive level of association, such as EPHB4 and PRDM16, which are risk loci for inflammatory bowel disease and rheumatoid arthritis, respectively. 57,74 The cumulative GRSs, which is a simple and intuitive approach to convert genetic data into a predictive measure of disease susceptibility, suggest that the differences in Takayasu arteritis prevalence have genetic bases. Although the GRS value of the African population was higher than expected, the data were in line with Takayasu prevalence described to date, being the highest in East Asia, Mexico, and South East Asia.…”

Section: Discussionmentioning

confidence: 99%

Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study

Ortiz-Fernández¹,

Saruhan‐Direskeneli²,

Alıbaz-Öner³

et al. 2021

The American Journal of Human Genetics

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Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 3 10 À5 ) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study

Ortiz-Fernández¹,

Saruhan‐Direskeneli²,

Alıbaz-Öner³

et al. 2021

The American Journal of Human Genetics

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“…NFKBID is critical for B cell development as shown in mouse model 35 . In addition to the association of THEMIS with celiac disease, two loci with rare variants have been reported of association with autoimmune diseases, i.e., the long intergenic non-protein coding RNA 1967 ( LINC01967 ) and C-X9-C motif containing 1 ( CMC1 ) locus at chr3p24.1 has been reported to be associated with multiple sclerosis 36 , and the small nucleolar RNA, C/D box 3F ( SNORD3F )/leucine zipper tumor suppressor 1 (LZTS1) antisense RNA 1 ( LZTS1-AS1 ) locus at chr8p21.3 which has been reported to be associated with rheumatoid arthritis 37 .…”

Section: Discussionmentioning

confidence: 99%

Genetic architecture of type 1 diabetes with low genetic risk score informed by 41 unreported loci

Bradfield

et al. 2021

Commun Biol

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Type 1 diabetes (T1D) patients with low genetic risk scores (GRS) may be non-autoimmune or autoimmune mediated by other genetic loci. The T1D-GRS2 provides us an opportunity to look into the genetic architecture of these patients. A total of 18,949 European individuals were included in this study, including 6599 T1D cases and 12,323 controls. 957 (14.5%) T1D patients were identified with low GRS (GRS < 8.43). The genome-wide association study on these patients identified 41 unreported loci. Two loci with common variants and 39 loci with rare variants were identified in this study. This study identified common SNPs associated with both low GRS T1D and expression levels of the interferon-α-induced MNDA gene, indicating the role of viral infection in T1D. Interestingly, 16 of the 41 unreported loci have been linked to autism spectrum disorder (ASD) by previous studies, suggesting that genes residing at these loci may underlie both T1D and autism.

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“…The next top SNP is rs1793958, located in COL2A1 (collagen type II alpha 1 chain), a gene involved in "regulation of immune response" biological process (GO:0050776). COL2A1 was found to be associated with rheumatoid arthritis [72] and with prostate carcinoma [73][74][75] in previous GWAS. On the other hand, the third highest SNP rs17174795 is located 1.4 kb apart from PTPRO (Protein Tyrosine Phosphatase Receptor type O), which has been suggested as a candidate tumour suppressor via the NF-Kappa B signalling pathway [76,77], and the transcription factor NF-Kappa B plays a central role in inflammatory airway diseases such as asthma [78].…”

Section: Discussionmentioning

confidence: 89%

Genome-Wide Association Study of Fluorescent Oxidation Products Accounting for Tobacco Smoking Status in Adults from the French EGEA Study

et al. 2022

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Oxidative stress (OS) is the main pathophysiological mechanism involved in several chronic diseases, including asthma. Fluorescent oxidation products (FlOPs), a global biomarker of damage due to OS, is of growing interest in epidemiological studies. We conducted a genome-wide association study (GWAS) of the FlOPs level in 1216 adults from the case-control and family-based EGEA study (mean age 43 years old, 51% women, and 23% current smokers) to identify genetic variants associated with FlOPs. The GWAS was first conducted in the whole sample and then stratified according to smoking status, the main exogenous source of reactive oxygen species. Among the top genetic variants identified by the three GWAS, those located in BMP6 (p = 3 × 10−6), near BMPER (p = 9 × 10−6), in GABRG3 (p = 4 × 10−7), and near ATG5 (p = 2 × 10−9) are the most relevant because of both their link to biological pathways related to OS and their association with several chronic diseases for which the role of OS in their pathophysiology has been pointed out. BMP6 and BMPER are of particular interest due to their involvement in the same biological pathways related to OS and their functional interaction. To conclude, this study, which is the first GWAS of FlOPs, provides new insights into the pathophysiology of chronic OS-related diseases.

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Studying the effects of haplotype partitioning methods on the RA-associated genomic results from the North American Rheumatoid Arthritis Consortium (NARAC) dataset

Abstract: Graphical abstract

Cited by 12 publications

References 144 publications

Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study

Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study

Genetic architecture of type 1 diabetes with low genetic risk score informed by 41 unreported loci

Genome-Wide Association Study of Fluorescent Oxidation Products Accounting for Tobacco Smoking Status in Adults from the French EGEA Study

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