title: Association of SNPs rs6498169 and rs10984447 with multiple sclerosis in Saudi patients: a model of the usefulness of familial aggregates in identifying genetic linkage in a multifactorial disease.
abstract: OBJECTIVE
  Genome-Wide association studies (GWAS) showed an association between subset of single-nucleotide polymorphism (SNPs) and multiple sclerosis. Our study aims to study this association in Saudi familial multiple sclerosis patients.
  
  
  METHODS
  Four subject groups were used in this study: sporadic MS (MS patients without family history), FMS (MS patients who have at least one family member diagnosed with MS), related controls (relatives of FMS patients who appear to be free of the disease) and independent controls (healthy volunteers). Subjects were genotyped for 15 SNPs. The variation in the genotype distribution was analyzed across study groups by using logistic regression.
  
  
  RESULTS
  342 subjects were included. 99 were in the sporadic MS group, 22 were FMS, 89 were related control, and 132 were independent control. SNPS rs3135388, rs7577363, rs1321172, rs6897932, rs6498169, rs12487066, and rs4763655were associated with MS when MS and independent control groups were compared. Same SNPS were identified but with stronger association when the FMS and independent control groups were compared. Finally, when the patients and the controls were selected from a much more homogenous genetic pool from which it would be expected that only SNPs highly linked to MS would persist, only two SNPs rs6498169[OR 4.26, CI (1.17 - 15.51)];, and rs10984447 [OR 13.63, CI(1.54, 120.83) ][were associated with MS.
  
  
  CONCLUSIONS
  Our results suggest that using a more homogenous genetic pool of cases and controls could help to identify the most significant MS-associated SNPs. Our finding is in agreement with other studies including larger sample size and more diverse populations.
authors.affiliation: King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. jumahm@ngha.med.sa
authors.forename: M
authors.initials: M
authors.lastname: Al Jumah
authors.forename: M
authors.initials: M
authors.lastname: Al Balwi
authors.forename: M
authors.initials: M
authors.lastname: Hussein
authors.forename: S
authors.initials: S
authors.lastname: Kojan
authors.forename: A
authors.initials: A
authors.lastname: Al Khathaami
authors.forename: M
authors.initials: M
authors.lastname: Al Fawaz
authors.forename: B
authors.initials: B
authors.lastname: Al Muzaini
authors.forename: A
authors.initials: A
authors.lastname: Jawhary
authors.forename: I
authors.initials: I
authors.lastname: Al Abdulkareem
mesh_terms: D000328:Adult; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012107:Research Design; D012529:Saudi Arabia