What Have We Learned From Family-Based Studies About Spondyloarthritis?
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 m...
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Published in | Frontiers in genetics Vol. 12; p. 671306 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media
03.06.2021
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 PMCID: PMC8209510 Reviewed by: Paul Lasko, McGill University, Canada; Roberta Ramonda, University of Padua, Italy This article was submitted to Genetics of Common and Rare Diseases, a section of the journal Frontiers in Genetics Edited by: Fabiana Paladini, Sapienza University of Rome, Italy |
ISSN: | 1664-8021 1664-8021 |
DOI: | 10.3389/fgene.2021.671306 |