title: Genome-wide analysis identifies a quantitative trait locus in the MHC class II region associated with generalized vitiligo age of onset.
abstract: Generalized vitiligo is a common autoimmune disease in which acquired patchy depigmentation of skin, hair, and mucous membranes results from loss of melanocytes from involved areas. Previous genetic analyses have focused on vitiligo susceptibility, and have identified a number of genes involved in disease risk. Age of onset of generalized vitiligo also involves a substantial genetic component, but has not previously been studied systematically. In this study, we report a genome-wide association study of vitiligo age of onset in 1,339 generalized vitiligo patients, with replication in an independent cohort of 677 cases. We identified a quantitative trait locus for vitiligo age of onset in the major histocompatibility complex (MHC) class II region, located near c6orf10-BTNL2 (rs7758128; P=8.14 × 10(-11)), a region that is also associated with generalized vitiligo susceptibility. In contrast, there was no association of vitiligo age of onset with any other MHC or non-MHC loci that are associated with vitiligo susceptibility. These findings highlight the differing roles played by genes involved in vitiligo susceptibility versus vitiligo age of onset, and illustrate that genome-wide analyses can be used to identify genes involved in quantitative aspects of disease natural history, as well as disease susceptibility per se.
authors.affiliation: Human Medical Genetics Program, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.forename: Stanca A
authors.initials: SA
authors.lastname: Birlea
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fain
authors.forename: Katherine
authors.initials: K
authors.lastname: Gowan
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Riccardi
authors.forename: Paulene J
authors.initials: PJ
authors.lastname: Holland
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Bennett
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Herbstman
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wallace
authors.forename: Wayne T
authors.initials: WT
authors.lastname: McCormack
authors.forename: E Helen
authors.initials: EH
authors.lastname: Kemp
authors.forename: David J
authors.initials: DJ
authors.lastname: Gawkrodger
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Weetman
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Leone
authors.forename: Alain
authors.initials: A
authors.lastname: Taïeb
authors.forename: Thomas
authors.initials: T
authors.lastname: Jouary
authors.forename: Khaled
authors.initials: K
authors.lastname: Ezzedine
authors.forename: Nanny
authors.initials: N
authors.lastname: van Geel
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
authors.forename: Andreas
authors.initials: A
authors.lastname: Overbeck
authors.forename: Richard A
authors.initials: RA
authors.lastname: Spritz
mesh_terms: D000328:Adult; D017668:Age of Onset; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D040641:Quantitative Trait Loci; D014820:Vitiligo / Q000235:genetics*