Dataset Information

HLA in isolated REM sleep behavior disorder and Lewy body dementia.

ABSTRACT:

Background and objectives

Isolated/idiopathic REM sleep behavior disorder (iRBD) and Lewy body dementia (LBD) are synucleinopathies that have partial genetic overlap with Parkinson's disease (PD). Previous studies have shown that neuroinflammation plays a substantial role in these disorders. In PD, specific residues of the human leukocyte antigen ( HLA ) were suggested to be associated with a protective effect. This study examined whether the HLA locus plays a similar role in iRBD, LBD and PD.

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.

SUBMITTER: Yu E

PROVIDER: S-EPMC9915822 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

<i>HLA</i> in isolated REM sleep behavior disorder and Lewy body dementia.

Yu Eric E Krohn Lynne L Ruskey Jennifer A JA Asayesh Farnaz F Spiegelman Dan D Shah Zalak Z Chia Ruth R Arnulf Isabelle I Hu Michele T M MTM Montplaisir Jacques Y JY Gagnon Jean-François JF Desautels Alex A Dauvilliers Yves Y Gigli Gian Luigi GL Valente Mariarosaria M Janes Francesco F Bernardini Andrea A Högl Birgit B Stefani Ambra A Ibrahim Abubaker A Heidbreder Anna A Sonka Karel K Dusek Petr P Kemlink David D Oertel Wolfgang W Janzen Annette A Plazzi Giuseppe G Antelmi Elena E Figorilli Michela M Puligheddu Monica M Mollenhauer Brit B Trenkwalder Claudia C Sixel-Döring Friederike F De Cock Valérie Cochen VC Ferini-Strambi Luigi L Dijkstra Femke F Viaene Mineke M Abril Beatriz B Boeve Bradley F BF Rouleau Guy A GA Postuma Ronald B RB Scholz Sonja W SW Gan-Or Ziv Z

medRxiv : the preprint server for health sciences 20230403

<h4>Background and objectives</h4>Isolated/idiopathic REM sleep behavior disorder (iRBD) and Lewy body dementia (LBD) are synucleinopathies that have partial genetic overlap with Parkinson's disease (PD). Previous studies have shown that neuroinflammation plays a substantial role in these disorders. In PD, specific residues of the human leukocyte antigen ( <i>HLA</i> ) were suggested to be associated with a protective effect. This study examined whether the <i>HLA</i> locus plays a similar role ...[more]

PMID: 36778313

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Dataset Information

HLA in isolated REM sleep behavior disorder and Lewy body dementia.

Background and objectives

Methods

Results

Discussion

Publications

<i>HLA</i> in isolated REM sleep behavior disorder and Lewy body dementia.

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Dataset Information

HLA in isolated REM sleep behavior disorder and Lewy body dementia.

Background and objectives

Methods

Results

Discussion

Publications

&lt;i&gt;HLA&lt;/i&gt; in isolated REM sleep behavior disorder and Lewy body dementia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

<i>HLA</i> in isolated REM sleep behavior disorder and Lewy body dementia.