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Review
. 2022 Nov 15:372:577957.
doi: 10.1016/j.jneuroim.2022.577957. Epub 2022 Aug 29.

Genetics of neurosarcoidosis

Abigail Hardin  1 , Bryan Dawkins  1 , Nathan Pezant  1 , Astrid Rasmussen  1 , Courtney Montgomery  2
Affiliations
Review

Genetics of neurosarcoidosis

Abigail Hardin et al. J Neuroimmunol. .

Abstract

Sarcoidosis is a systemic, inflammatory, granulomatous disease characterized by great variability in organ involvement, clinical course, and severity. While pulmonary manifestations are almost universal, the central and peripheral nervous systems can also be affected. Neurosarcoidosis occurs in ∼5-15% of cases and is among the manifestations with the highest morbidity and mortality. It is known that sarcoidosis has genetic underpinnings and while multiple studies aimed at identifying associations to sarcoidosis susceptibility and prognosis, very few studies have focused on neurosarcoidosis. This review summarizes the genetic studies to date, compares and contrasts those findings with other genetic effects in sarcoidosis, and offers ideas for moving the field forward.

Keywords: Genetic association; HLA-DRB1; Neurosarcoidosis; Zinc-Finger proteins.

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Conflict of interest statement

Declaration of Competing Interest None.

Figures

Figure 1.
Figure 1.
Potential roles of ZNF592 in sarcoidosis and neurosarcoidosis.
Figure 2.
Figure 2.
Manhattan Plot of GWAS of neurosarcoidosis. The red line indicates genome-wide significance (p<5 × 10−8) and the blue line is suggestive significance (p<1 × 10−5). The blue circles correspond to regions containing F5, RP11–462L8.1, and AMN1 on Chromosomes 1, 10, and 12, respectively, and the red circle corresponds to the 15q25 region containing ZNF592.
Figure 3.
Figure 3.
Clustering of organ involvement in 242 European American (Panel A) and 900 African American (Panel B) sarcoidosis patients. Sample coordinates represent the first two MCA principal dimensions (Dim1 and Dim2). The proportion of the variance explained by each principal dimension is given in parentheses as a percentage. The colors and shapes represent cluster membership for the various organs involved. The clusters including neurological involvement are highlighted (green circle) and labeled. The primary, distinguishing organ systems in each of the other clusters are as follows: Panel A, 1-muscle and joint, 2-skin, 3-neurological and ocular, 4-renal, 5-cardiac, 6-liver and spleen; Panel B, 1-extra-thoracic lymph nodes, 2-skin, 3-eye, 4-neurological, 5-renal and cardiac, 6-liver and spleen, 7-muscle.
See this image and copyright information in PMC

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