All in the family: a population-scale perspective on genetic networks of autoimmune disease
Arielle Klepper, Mark S. Anderson
Arielle Klepper, Mark S. Anderson
View: Text | PDF
Commentary

All in the family: a population-scale perspective on genetic networks of autoimmune disease

Abstract

Autoimmune diseases share a genetic predisposition, and GWAS have identified certain HLA haplotypes as components of susceptibility. In this issue of the JCI, Eriksson et al. leveraged population-scale registry data from Sweden, encompassing 6.3 million individuals in combination with paired relatedness data from a remarkable 3.84 million sibling pairs drawn from 1.57 million nuclear families to create a unified model of the shared genetic risk across 22 common and rare autoimmune diseases. The resulting network of pairwise genetic relationships demonstrated that genetic predisposition alone could not explain the full spectrum of autoimmunity. Analyses exposed distinct patterns, confirmed expected genetic relationships, and revealed unexpected findings. By looking into the family to quantify shared genetic liability at a remarkable scale, this study not only reinforces established genetic components of autoimmune disease but also highlights variation that lacks shared genetic architecture, paving the way for future study of environmental mechanisms in autoimmunity.

Authors

Arielle Klepper, Mark S. Anderson

×

Figure 1

Genetic patterns underlying autoimmune diseases.

Options: View larger image (or click on image) Download as PowerPoint
Genetic patterns underlying autoimmune diseases. (A) Established pattern...
(A) Established patterns: some diseases, such as multiple sclerosis (MS) and type 1 diabetes (T1D), aggregate in families (left). Other autoimmune diseases are known to aggregate in individuals, in part due to shared genetic susceptibility, such as HLA variants common to both T1D and celiac disease (center), or clustering of connective tissue diseases in individuals, e.g., systemic lupus erythematosus and Sjögren’s syndrome (right). (B) Eriksson et al. (3) compared susceptibility across 22 autoimmune diseases in a large Swedish cohort, leveraging sibling registry data to construct a matrix of pairwise genetic correlations. Their findings confirm some prior insights about genetic patterns, such as the clustering of tissue-specific diseases, but they also unearth fresh insights into variation among autoimmune diseases, as summarized in the highlighted findings. GI, gastrointestinal.