title: Genome-wide association study identifies PERLD1 as asthma candidate gene.
abstract: BACKGROUND
  Recent genome-wide association studies (GWAS) for asthma have been successful in identifying novel associations which have been well replicated. The aim of this study is to identify the genetic variants that influence predisposition towards asthma in an ethnic Chinese population in Singapore using a GWAS approach.
  
  
  METHODS
  A two-stage GWAS was performed in case samples with allergic asthma, and in control samples without asthma and atopy. In the discovery stage, 490 case and 490 control samples were analysed by pooled genotyping. Significant associations from the first stage were evaluated in a replication cohort of 521 case and 524 control samples in the second stage. The same 980 samples used in the discovery phase were also individually genotyped for purposes of a combined analysis. An additional 1445 non-asthmatic atopic control samples were also genotyped.
  
  
  RESULTS
  19 promising SNPs which passed our genome-wide P value threshold of 5.52 × 10-8 were individually genotyped. In the combined analysis of 1011 case and 1014 control samples, SNP rs2941504 in PERLD1 on chromosome 17q12 was found to be significantly associated with asthma at the genotypic level (P = 1.48 × 10-6, ORAG = 0.526 (0.369-0.700), ORAA = 0.480 (0.361-0.639)) and at the allelic level (P = 9.56 × 10-6, OR = 0.745 (0.654-0.848)). These findings were found to be replicated in 3 other asthma GWAS studies, thus validating our own results. Analysis against the atopy control samples suggested that the SNP was associated with allergic asthma and not to either the asthma or allergy components. Genotyping of additional SNPs in 100 kb flanking rs2941504 further confirmed that the association was indeed to PERLD1. PERLD1 is involved in the modification of the glycosylphosphatidylinositol anchors for cell surface markers such as CD48 and CD59 which are known to play multiple roles in T-cell activation and proliferation.
  
  
  CONCLUSIONS
  These findings reveal the association of a PERLD1 as a novel asthma candidate gene and reinforce the involvement of genes on the 17q12-21 chromosomal region in the etiology of asthma.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Ramani
authors.initials: R
authors.lastname: Anantharaman
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Andiappan
authors.forename: Pallavi Parate
authors.initials: PP
authors.lastname: Nilkanth
authors.forename: Bani Kaur
authors.initials: BK
authors.lastname: Suri
authors.forename: De Yun
authors.initials: de Y
authors.lastname: Wang
authors.forename: Fook Tim
authors.initials: FT
authors.lastname: Chew
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D001249:Asthma / Q000235:genetics*; D002265:Carboxylic Ester Hydrolases; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D012846:Singapore / Q000453:epidemiology; D055815:Young Adult
chemical_list: D011956:Receptors, Cell Surface; D002265:Carboxylic Ester Hydrolases; C476212:PGAP3 protein, human