Whole-genome single nucleotide polymorphism-based linkage analysis in spondyloarthritis multiplex families reveals a new susceptibility locus in 13q13

Costantino, Félicie; Chaplais, Emmanuel; Leturcq, Tifenn; Said‐Nahal, Roula; Zinovieva, Elena; Zélénika, Diana; Gut, Marta; Charon, Céline; Chiocchia, Gilles; Bréban, Maxime; Garchon, Henri‐Jean

doi:10.1136/annrheumdis-2015-207720

Cited by 10 publications

(4 citation statements)

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“…Quality control measures were applied to the genome-wide genotype data as previously described 15. Briefly, after removing Mendelian errors and subtle genotyping inconsistencies, SNPs with low genotyping rate (<95%) or with significant deviation from Hardy-Weinberg proportions (p<1×10 −3 ) were removed.…”

Section: Methodsmentioning

confidence: 99%

A family-based genome-wide association study reveals an association of spondyloarthritis withMAPK14

et al. 2016

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Section: Methodsmentioning

confidence: 99%

A family-based genome-wide association study reveals an association of spondyloarthritis withMAPK14

et al. 2016

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“…One limitation of linkage studies is that they cannot locate disease-associated loci on a fine scale. To try to circumvent this issue, a more recent linkage analysis used a high-density panel of SNPs and identified a new locus significantly linked with SpA was identified on 13q13 ( Costantino et al, 2016 ). However, despite the higher density of marker, the disease interval could not be restricted to less than 1.4 Mb and further investigations are needed to identify causal variant(s) in this region.…”

Section: Family-based Approaches For Identification Of Genes Of Susceptibility To Spamentioning

confidence: 99%

What Have We Learned From Family-Based Studies About Spondyloarthritis?

et al. 2021

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Spondyloarthritis (SpA) is a chronic inflammatory disorder with a high familial aggregation, emphasizing the existence of genetic susceptibility factors. In the last decades, family-based studies have contributed to better understand the genetic background of SpA, in particular by showing that the most likely model of transmission is oligogenic with multiplicative effects. Coexistence of different SpA subtypes within families also highlighted the complex interplay between all subtypes. Several whole-genome linkage analyses using sib-pairs or multiplex families were performed in the 1990s to try to identify genetic susceptibility factors besides HLA-B27. Unfortunately, no consistent results were obtained and family-based studies have been progressively set aside in favor of case-control designs. In particular, case-control genome-wide association studies allowed the identification of more than 40 susceptibility regions. However, all these loci explain only a small fraction of disease predisposition. Several hypotheses have been advanced to account for this unexplained heritability, including rare variants involvement, leading to a renewed interest in family-based designs, which are probably more powerful in the detection of such variants. In this review, our purpose is to summarize what has been learned to date regarding SpA genetics from family-based studies, with a special focus on recent identification of rare associated variants through next-generation sequencing studies.

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“…To try to circumvent this issue, a more recent linkage analysis used a high-density panel of SNPs. A new locus significantly linked with SpA was identified on 13q13 but the disease interval could not be restricted to < 1.4 Mb (51). Thus, linkage analysis can be seen as a preliminary step to highlight regions of interest which can be deep-resequenced.…”

Section: Genetics Of Spondyloarthritismentioning

confidence: 99%

Genetics and Functional Genomics of Spondyloarthritis

2018

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Spondyloarthritis (SpA) is a chronic inflammatory disorder with high heritability but with complex genetics. It encompasses several entities that share common clinical features. Most of the genetic studies in SpA have been restricted to ankylosing spondylitis (AS), the prototypical form of SpA. However, there is growing evidence of shared genetic background between all the SpA subtypes and also with some other immune-mediated diseases. The most important part of SpA heritability comes from the HLA-B27 allele in the major histocompatibility complex (MHC) that explains around 25% of the attributable heredity. Several other loci outside of the MHC have been shown to be involved in the disease. However, all these non-MHC loci explain only a small additional fraction of disease predisposition. Thus, a substantial fraction of SpA genetic basis remains poorly understood. Gene expression profiling is a complementary approach to elucidate the underlying mechanisms and pathways that drive the disease. Several expression profiling studies have been undertaken in SpA. However, results have been quite disappointing with little overlap between the studies largely due to the small sample sizes, resulting in limited power to discover small effects. In this review, we summarize current knowledge on genetic findings concerning SpA and we describe strategic approaches for identification of additional variants, with a focus on rare variants in familial forms. We also provide an overview of gene expression studies in SpA and discuss the possibilities offered by high-throughput RNA sequencing technologies, in particular in sorted cells. Finally, issues in establishing molecular mechanisms underlying genetic association hits and potential translational applications will be addressed.

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Whole-genome single nucleotide polymorphism-based linkage analysis in spondyloarthritis multiplex families reveals a new susceptibility locus in 13q13

Abstract: We report here for the first time a significant linkage between 13q13 and SpA. Identification of susceptibility factor inside this chromosomal region through targeted sequencing in linked families is underway.

Cited by 10 publications

References 48 publications

A family-based genome-wide association study reveals an association of spondyloarthritis withMAPK14

A family-based genome-wide association study reveals an association of spondyloarthritis withMAPK14

What Have We Learned From Family-Based Studies About Spondyloarthritis?

Genetics and Functional Genomics of Spondyloarthritis

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