title: Natural selection in a bangladeshi population from the cholera-endemic ganges river delta.
abstract: As an ancient disease with high fatality, cholera has likely exerted strong selective pressure on affected human populations. We performed a genome-wide study of natural selection in a population from the Ganges River Delta, the historic geographic epicenter of cholera. We identified 305 candidate selected regions using the composite of multiple signals (CMS) method. The regions were enriched for potassium channel genes involved in cyclic adenosine monophosphate-mediated chloride secretion and for components of the innate immune system involved in nuclear factor κB (NF-κB) signaling. We demonstrate that a number of these strongly selected genes are associated with cholera susceptibility in two separate cohorts. We further identify repeated examples of selection and association in an NF-κB/inflammasome-dependent pathway that is activated in vitro by Vibrio cholerae. Our findings shed light on the genetic basis of cholera resistance in a population from the Ganges River Delta and present a promising approach for identifying genetic factors influencing susceptibility to infectious diseases.
authors.affiliation: Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. elinor@broadinstitute.org
authors.forename: Elinor K
authors.initials: EK
authors.lastname: Karlsson
authors.forename: Jason B
authors.initials: JB
authors.lastname: Harris
authors.forename: Shervin
authors.initials: S
authors.lastname: Tabrizi
authors.forename: Atiqur
authors.initials: A
authors.lastname: Rahman
authors.forename: Ilya
authors.initials: I
authors.lastname: Shlyakhter
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Colm
authors.initials: C
authors.lastname: O'Dushlaine
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.forename: Sameer
authors.initials: S
authors.lastname: Gupta
authors.forename: Fahima
authors.initials: F
authors.lastname: Chowdhury
authors.forename: Alaullah
authors.initials: A
authors.lastname: Sheikh
authors.forename: Ok Sarah
authors.initials: OS
authors.lastname: Shin
authors.forename: Crystal
authors.initials: C
authors.lastname: Ellis
authors.forename: Christine E
authors.initials: CE
authors.lastname: Becker
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Stuart
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
authors.forename: Edward T
authors.initials: ET
authors.lastname: Ryan
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
authors.forename: Regina C
authors.initials: RC
authors.lastname: Larocque
mesh_terms: D002771:Cholera / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics; D045483:Rivers; D012641:Selection, Genetic / Q000235:genetics; D014734:Vibrio cholerae / Q000472:pathogenicity
chemical_list: D058847:Inflammasomes; D016328:NF-kappa B