Association study reveals novel risk loci for sporadic inclusion body myositis

M Johari; M Arumilli; J Palmio; M Savarese; G Tasca; M Mirabella; N Sandholm; H Lohi; P Hackman; B Udd

doi:10.1111/ene.13244

Association study reveals novel risk loci for sporadic inclusion body myositis

Eur J Neurol. 2017 Apr;24(4):572-577. doi: 10.1111/ene.13244. Epub 2017 Feb 24.

Authors

M Johari¹, M Arumilli^{1

2

3}, J Palmio⁴, M Savarese¹, G Tasca⁵, M Mirabella⁶, N Sandholm^{1

7

8}, H Lohi^{1

2

3}, P Hackman¹, B Udd^{1

4

9}

Affiliations

¹ Folkhälsan Institute of Genetics, Medicum, University of Helsinki, Helsinki, Finland.
² Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
³ Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
⁴ Neuromuscular Research Center, Tampere University and University Hospital, Tampere, Finland.
⁵ Institute of Neurology, Policlinico 'A. Gemelli' Foundation University Hospital, Rome, Italy.
⁶ Institute of Neurology, Catholic University School of Medicine, Rome, Italy.
⁷ Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁸ Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
⁹ Department of Neurology, Vaasa Central Hospital, Vaasa, Finland.

PMID: 28233382
DOI: 10.1111/ene.13244

Abstract

Background and purpose: The aim was to identify potential genetic risk factors associated with sporadic inclusion body myositis (sIBM).

Methods: An association based case-control approach was utilized on whole exome sequencing data of 30 Finnish sIBM patients and a control cohort (n = 193). A separate Italian cohort of sIBM patients (n = 12) was used for evaluation of the results.

Results: Seven single nucleotide polymorphisms were identified in five genes that have a considerably higher observed frequency in Finnish sIBM patients compared to the control population, and the previous association of the genetic human leukocyte antigen region was confirmed.

Conclusions: All seven identified variants could individually or in combination increase the susceptibility for sIBM.

Keywords: HLA; association study; case−control study; genetic risk factors; risk loci; sphingolipids; sporadic inclusion body myositis; whole exome sequencing.

MeSH terms

Aged
Alleles
Case-Control Studies
Cohort Studies
Exome
Exome Sequencing
Female
Gene Frequency
Genetic Association Studies
Genetic Loci
Genetic Predisposition to Disease*
Humans
Male
Middle Aged
Myositis, Inclusion Body / genetics*
Polymorphism, Single Nucleotide*
Risk