Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Research output: Contribution to journalJournal articleResearchpeer-review

  • Lavinia Paternoster
  • Marie Standl
  • Chih-Mei Chen
  • Adaikalavan Ramasamy
  • Klaus Bønnelykke
  • Liesbeth Duijts
  • Manuel A Ferreira
  • Alexessander Couto Alves
  • Thyssen, Jacob Pontoppidan
  • Eva Albrecht
  • Hansjörg Baurecht
  • Bjarke Feenstra
  • Patrick M A Sleiman
  • Pirro Hysi
  • Nicole M Warrington
  • Ivan Curjuric
  • Ronny Myhre
  • John A Curtin
  • Maria M Groen-Blokhuis
  • Marjan Kerkhof
  • Annika Sääf
  • Andre Franke
  • David Ellinghaus
  • Regina Fölster-Holst
  • Emmanouil Dermitzakis
  • Stephen B Montgomery
  • Holger Prokisch
  • Katharina Heim
  • Anna-Liisa Hartikainen
  • Anneli Pouta
  • Juha Pekkanen
  • Alexandra I F Blakemore
  • Jessica L Buxton
  • Marika Kaakinen
  • David L Duffy
  • Pamela A Madden
  • Andrew C Heath
  • Grant W Montgomery
  • Philip J Thompson
  • Melanie C Matheson
  • Peter Le Souëf
  • Beate St Pourcain
  • George Davey Smith
  • John Henderson
  • John P Kemp
  • Nicholas J Timpson
  • Panos Deloukas
  • Linneberg, Allan René
  • Torkil Menné
  • Bisgaard, Hans
  • Australian Asthma Genetics Consortium (AAGC)
Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.
Original languageEnglish
JournalNature Genetics
Volume44
Issue number2
Pages (from-to)187-192
ISSN1061-4036
DOIs
Publication statusPublished - 25 Dec 2011

ID: 40145036