A meta-analysis uncovers the first sequence variant conferring risk of Bell’s palsy, 2021, Skuladottir et al

[forestglip]

A meta-analysis uncovers the first sequence variant conferring risk of Bell’s palsy

Spoiler: Authors

Astros Th Skuladottir 1,✉, Gyda Bjornsdottir 1, Gudmar Thorleifsson 1, G Bragi Walters 1,2, Muhammad Sulaman Nawaz 1,2, Kristjan Helgi Swerford Moore 1, Pall I Olason 1, Thorgeir E Thorgeirsson 1, Brynja Sigurpalsdottir 1,3, Gardar Sveinbjornsson 1, Hannes P Eggertsson 1, Sigurdur H Magnusson 1, Asmundur Oddsson 1, Anna Bjornsdottir 4, Arnor Vikingsson 5, Olafur A Sveinsson 5, Maria G Hrafnsdottir 5, Gudrun R Sigurdardottir 4, Bjarni V Halldorsson 1, Thomas Folkmann Hansen 6, Helene Paarup 7, Christian Erikstrup 8, Kaspar Nielsen 9, Mads Klokker 10, Mie Topholm Bruun 7, Erik Sorensen 10, Karina Banasik 6, Kristoffer S Burgdorf 10, Ole Birger Pedersen 11, Henrik Ullum 10, Ingileif Jonsdottir 1,2, Hreinn Stefansson 1, Kari Stefansson 1,2

Published: 18 February 2021

[Line breaks added]

Abstract
Bell’s palsy is the most common cause of unilateral facial paralysis and is defined as an idiopathic and acute inability to control movements of the facial muscles on the affected side.

While the pathogenesis remains unknown, previous studies have implicated post-viral inflammation and resulting compression of the facial nerve. Reported heritability estimates of 4–14% suggest a genetic component in the etiology and an autosomal dominant inheritance has been proposed.

Here, we report findings from a meta-analysis of genome-wide association studies uncovering the first unequivocal association with Bell’s palsy (rs9357446-A; P = 6.79 × 10−23, OR = 1.23; Ncases = 4714, Ncontrols = 1,011,520). The variant also confers risk of intervertebral disc disorders (P = 2.99 × 10−11, OR = 1.04) suggesting a common pathogenesis in part or a true pleiotropy.

Link | PDF (Scientific Reports) [Open Access]

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Requested to be posted by @Deanne NZ.

 

[forestglip]

They found clear evidence for this variant causing Bell's palsy from a meta-analysis of 4 GWAS's, all showing the same effect direction. But it's in an intergenic region, and they weren't able to associate it with any specific gene, so it's not clear what it does.

We were unable to determine a gene at 6p21.1 involved in Bell’s palsy pathology. However, the association of rs9357446-A with IDD brings up the possibility that the variant may confer risk of Bell’s palsy through an effect on cartilage and bone development. Alternatively, the association between Bell’s palsy, IDD, and reduced lung function may be a result of a true pleiotropy.

 

[duncan]

Bell’s palsy is the most common cause of unilateral facial paralysis and is defined as an idiopathic and acute inability to control movements of the facial muscles on the affected side.

Idiopathic? I thought Bell's palsy was tied into a handful of viruses and bacteria, e.g. herpes variants and borrelia.

 

[forestglip]

Idiopathic? I thought Bell's palsy was tied into a handful of viruses and bacteria, e.g. herpes variants and borrelia.

What it says is known about causes:

Bell’s palsy is still idiopathic since we do not know what causes it; there are no biomarkers to support the diagnosis and the diagnosis requires exclusion of any other cause of facial paralysis24. In Bell’s palsy, a viral infection is considered one of the possible causes8. The main treatment is corticosteroids, which supports the theory of edema induced entrapment neuropathy. The facial nerve traverses through the temporal bone (the facial canal) and branches to innervate the facial muscles. The narrowest part of the canal, the labyrinthine segment, is where most cases of compression occur, which may result in ischemic neuropathy of the facial nerve25.

 

[duncan]

I wonder why facial paralysis wouldn't be considered a biomarker. In some infections, rashes would be in and of themselves.

 

[Hutan]

This paper was interesting to read, especially with DecodeME on the horizon.



This is the Manhattan plot, with position on the chromosome on the x axis and p values on the y axis. And it's a really clear result - there are variants that are not puddling around at around 5 on the y-axis.

And yet, it is in an inter-genic region, so it's particularly unclear how it might be contributing to Bells Palsy. Clearly, there is a lot to know yet.

Also notable that the odds ratio of that particular variant with the highest p-value is relatively low even given the strong p-value. It was only 1.23 or something like that. So these variants are not the whole story.