Category: Parkinson's Disease: Genetics
Objective: To examine genetic association of HLA alleles and amino acid for isolated REM sleep behavior disorder (iRBD) and Lewy body dementia (LBD). We compare with results in Parkinson’s disease (PD).
Background: Recent studies have shown evidence for the association of HLA-DRB1 11V, 13H, 33H with PD. However, similar analysis in iRBD and LBD has not been examined in large cohorts.
Method: We performed association studies on 1,072 iRBD cases and 918 in-house controls along with an additional 8,587 publicly available controls of European ancestry from dbGap. We also analyzed 2,604 European LBD patients and 4,032 European controls. Using HIBAG, we imputed HLA alleles and amino acid from genotyping data. Statistical analysis was performed to examine the association of specific HLA alleles and amino acid with synucleinopathies. P-value threshold were corrected for multiple testing.
Results: DRB1 37S (OR = 0.76; 95%CI = [-0.43,-0.11]; p = 8.44*10-4) is associated with iRBD. No other allele or amino acid were associated with iRBD nor LBD. While the candidate amino acids in iRBD were different than the amino acid (DRB1 33H) in PD, the carrier frequency in iRBD cases and controls for 33H are 22% and 27% respectively. In LBD, the carrier frequency of DRB1 33H is 27%, the same as in cases and controls. When examining the effect of 33H (rs17879995) and 37S (rs16822820) as expression quantitative trait loci (eQTL) in the GTEx portal, 33H is associated with differential expression HLA-DQA2, HLA-DRB6, HLA-DRB1 in various brain tissues. 37S is associated in other brain tissues with HLA-DRB5, HLA-DQB1, HLA-DQA1.
Conclusion: DRB1 37S was found to be associated with reduced risk for iRBD. No alleles nor amino acid were found to be associated with LBD. No association to previous PD related HLA amino acids were detected in iRBD and LBD even though the carrier frequency is lower in cases for iRBD. This suggests that the HLA locus could play different roles in synucleinopathies. Further studies are needed to finemap the HLA locus.
To cite this abstract in AMA style:
E. Yu, L. Krohn, J. Ruskey, F. Asayesh, S. Laurent, D. Spiegelman, Z. Shah, I. Arnulf, M. Hu, J. Montplaisir, JF. Gagnon, A. Desautels, Y. Dauvilliers, G. Gigli, M. Valente, F. Janes, A. Bernardini, B. Högl, A. Stefani, A. Ibrahim, K. Sonka, D. Kemlink, W. Oertel, A. Janzen, G. Plazzi, E. Antelmi, M. Figorilli, M. Puligheddu, B. Mollenhauer, C. Trenkwalder, F. Sixel-Döring, V. Cochen, C. Monaca, A. Heidbreder, L. Ferini-Strambi, F. Dijkstra, M. Viaene, B. Abril, B. Boeve, G. Rouleau, R. Postuma, S. Scholz, Z. Gan-Or. Analysis of the HLA locus in isolated REM sleep behavior disorder and Lewy body dementia [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/analysis-of-the-hla-locus-in-isolated-rem-sleep-behavior-disorder-and-lewy-body-dementia/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-the-hla-locus-in-isolated-rem-sleep-behavior-disorder-and-lewy-body-dementia/