TY - JOUR
T1 - Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
AU - Paternoster, Lavinia
AU - Standl, Marie
AU - Chen, Chih-Mei
AU - Ramasamy, Adaikalavan
AU - Bønnelykke, Klaus
AU - Duijts, Liesbeth
AU - Ferreira, Manuel A
AU - Alves, Alexessander Couto
AU - Thyssen, Jacob P
AU - Albrecht, Eva
AU - Baurecht, Hansjörg
AU - Feenstra, Bjarke
AU - Sleiman, Patrick M A
AU - Hysi, Pirro
AU - Warrington, Nicole M
AU - Curjuric, Ivan
AU - Myhre, Ronny
AU - Curtin, John A
AU - Groen-Blokhuis, Maria M
AU - Kerkhof, Marjan
AU - Sääf, Annika
AU - Franke, Andre
AU - Ellinghaus, David
AU - Fölster-Holst, Regina
AU - Dermitzakis, Emmanouil
AU - Montgomery, Stephen B
AU - Prokisch, Holger
AU - Heim, Katharina
AU - Hartikainen, Anna-Liisa
AU - Pouta, Anneli
AU - Pekkanen, Juha
AU - Blakemore, Alexandra I F
AU - Buxton, Jessica L
AU - Kaakinen, Marika
AU - Duffy, David L
AU - Madden, Pamela A
AU - Heath, Andrew C
AU - Montgomery, Grant W
AU - Thompson, Philip J
AU - Matheson, Melanie C
AU - Le Souëf, Peter
AU - St Pourcain, Beate
AU - Smith, George Davey
AU - Henderson, John
AU - Kemp, John P
AU - Timpson, Nicholas J
AU - Deloukas, Panos
AU - Ring, Susan M
AU - McArdle, Wendy
AU - Palmer, Lyle J
AU - Australian Asthma Genetics Consortium (AAGC)
AU - The Genetics of Overweight Young Adults (GOYA) Consortium
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
U2 - 10.1038/ng.1017
DO - 10.1038/ng.1017
M3 - Article (Academic Journal)
C2 - 22197932
VL - 44
SP - 187
EP - 192
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -