title: Genetic variation in SENP1 and ANP32D as predictors of chronic mountain sickness.
abstract: Chronic mountain sickness (CMS) is a serious illness that affects life-long high-altitude residents. A recent study analyzed whole genome sequence data from residents of Cerro de Pasco (Peru) in an effort to identify the genetic basis of CMS and reported SENP1 (rs7963934) and ANP32D (rs72644851) to show signatures consistent with natural selection and protective against CMS (Zhou et al. 2013 ). We set out to replicate these observations in two Andean cohorts from Cerro de Pasco, consisting of 84 CMS cases and 91 healthy controls in total. We report evidence of association for rs7963934 (SENP1) in the combined cohorts (meta-analysis p=8.8x10(-4) OR 2.91, CI 1.56-5.5, I=0). The direction of effect was the same as in the original publication. We did not observe any significant correlation between rs72644851 (ANP32D) and the CMS phenotype, within or across cohorts (meta-analysis p=0.204, OR 1.37, CI 0.84-2.241, I=0). Our results provide independent evidence in support of a role for SENP1 in CMS in individuals of Quechua ancestry and suggest the SENP1 and ANP32D signatures of selection are in tight linkage disequilibrium (LD).
authors.affiliation: 1 Department of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Amy M
authors.initials: AM
authors.lastname: Cole
authors.forename: Nayia
authors.initials: N
authors.lastname: Petousi
authors.forename: Gianpiero L
authors.initials: GL
authors.lastname: Cavalleri
authors.forename: Peter A
authors.initials: PA
authors.lastname: Robbins
mesh_terms: D000328:Adult; D000532:Altitude Sickness / Q000235:genetics*; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics*; D010568:Peru; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*
chemical_list: C490336:ANP32E protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D010750:Phosphoproteins; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases