HLA in isolated REM sleep behavior disorder and Lewy body dementia.
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Yu Eric, Krohn Lynne, Ruskey Jennifer A, Asayesh Farnaz, Spiegelman Dan, Shah Zalak, Chia Ruth, Arnulf Isabelle, Hu Michele T M, Montplaisir Jacques Y, Gagnon Jean-François, Desautels Alex, Dauvilliers Yves, Gigli Gian Luigi, Valente Mariarosaria, Janes Francesco, Bernardini Andrea, Högl Birgit, Stefani Ambra, Ibrahim Abubaker, Heidbreder Anna, Sonka Karel, Dusek Petr, Kemlink David, Oertel Wolfgang, Janzen Annette, Plazzi Giuseppe, Antelmi Elena, Figorilli Michela, Puligheddu Monica, Mollenhauer Brit, Trenkwalder Claudia, Sixel-Döring Friederike, De Cock Valérie Cochen, Ferini-Strambi Luigi, Dijkstra Femke, Viaene Mineke, Abril Beatriz, Boeve Bradley F, Rouleau Guy A, Postuma Ronald B, Scholz Sonja W, International LBD Genomics Consortium, Gan-Or Ziv
Аннотация
METHODS: We performed HLA imputation on iRBD genotyping data (1,072 patients and 9,505 controls) and LBD whole-genome sequencing (2,604 patients and 4,032 controls) using the multi-ethnic HLA reference panel v2 from the Michigan Imputation Server. Using logistic regression, we tested the association of HLA alleles, amino acids and haplotypes with disease susceptibility. We included age, sex and the top 10 principal components as covariates. We also performed an omnibus test to examine which HLA residue positions explain the most variance.
RESULTS: In iRBD, HLA-DRB1 *11:01 was the only allele passing FDR correction (OR=1.57, 95% CI=1.27-1.93, p =2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR=1.26, 95%CI=1.12-1.41, p =8.76e-05), 70Q (OR=0.81, 95% CI=0.72-0.91, p =3.65e-04) and 71R (OR=1.21, 95% CI=1.08-1.35, p =1.35e-03). In HLA-DRB1 , position 71 ( p omnibus =0.00102) and 70 ( p omnibus =0.00125) were associated with iRBD. We found no association in LBD.
DISCUSSION: This study identified an association between HLA-DRB1 11:01 and iRBD, distinct from the previously reported association in PD. Therefore, the HLA locus may play different roles across synucleinopathies. Additional studies are required better to understand HLA's role in iRBD and LBD.