title: Exploring the CLEC16A gene reveals a MS-associated variant with correlation to the relative expression of CLEC16A isoforms in thymus.
abstract: Genomewide association studies have implicated the CLEC16A gene in several autoimmune diseases, including multiple sclerosis (MS) and type 1 diabetes. However, the most associated single-nucleotide polymorphism (SNP) varies, and causal variants are still to be defined. In MS, two SNPs in partial linkage disequilibrium with each other, rs6498169 and rs12708716, have been validated at genomewide significance level. To explore the CLEC16A association in MS in more detail, we genotyped 57 SNPs in 807 Norwegian MS patients and 1027 Norwegian controls. Six highly associated SNPs emerged and were then replicated in two large independent sample sets (Norwegian and British), together including 1153 MS trios, 2308 MS patients and 4044 healthy controls. In combined analyses, SNP rs12708716 gave the strongest association signal in MS (P=5.3 x 10⁻⁸, odds ratio 1.18, 95% confidence interval=1.11-1.25), and was found to be superior to the other SNP associations in conditional logistic regression analyses. Expression analysis revealed that rs12708716 genotype was significantly associated with the relative expression levels of two different CLEC16A transcripts in thymus (P=0.004), but not in blood, possibly implying a thymus- or cell-specific splice regulation.
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway. ilmero@rr-research.no
authors.forename: I-L
authors.initials: IL
authors.lastname: Mero
authors.forename: M
authors.initials: M
authors.lastname: Ban
authors.forename: Å R
authors.initials: ÅR
authors.lastname: Lorentzen
authors.forename: C
authors.initials: C
authors.lastname: Smestad
authors.forename: E G
authors.initials: EG
authors.lastname: Celius
authors.forename: H
authors.initials: H
authors.lastname: Sæther
authors.forename: H
authors.initials: H
authors.lastname: Saeedi
authors.forename: M K
authors.initials: MK
authors.lastname: Viken
authors.forename: B
authors.initials: B
authors.lastname: Skinningsrud
authors.forename: D E
authors.initials: DE
authors.lastname: Undlien
authors.forename: J
authors.initials: J
authors.lastname: Aarseth
authors.forename: K-M
authors.initials: KM
authors.lastname: Myhr
authors.forename: S
authors.initials: S
authors.lastname: Granum
authors.forename: A
authors.initials: A
authors.lastname: Spurkland
authors.forename: S
authors.initials: S
authors.lastname: Sawcer
authors.forename: A
authors.initials: A
authors.lastname: Compston
authors.forename: B A
authors.initials: BA
authors.lastname: Lie
authors.forename: H F
authors.initials: HF
authors.lastname: Harbo
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D013950:Thymus Gland / Q000378:metabolism*; D055815:Young Adult
chemical_list: C522505:CLEC16A protein, human; D037181:Lectins, C-Type; D009004:Monosaccharide Transport Proteins; D020033:Protein Isoforms