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

L Paternoster; M Standl; CM Chen; A Ramasamy; K Bonnelykke; Liesbeth Duijts; MA Ferreira; AC Alves; JP Thyssen; E Albrecht; H Baurecht; BWA Feenstra; PMA Sleiman; P Hysi; NM Warrington; I Curjuric; R Myhre; JA Curtin; MM Groen-Blokhuis; M Kerkhof; A Saaf; A Franke; D Ellinghaus; R Folster-Holst; E Dermitzakis; SB Montgomery; H Prokisch; K Heim; AL Hartikainen; A Pouta; J Pekkanen; AIF Blakemore; JL Buxton; M Kaakinen; DL Duffy; PA Madden; AC Heath; GW Montgomery; PJ Thompson; MC Matheson; P Le Souef; B St Pourcain; GD Smith; J Henderson; JP Kemp; NJ Timpson; P Deloukas; SM Ring; HE Wichmann; M Muller-Nurasyid; N Novak; N Klopp; E Rodriguez; W McArdle; A Linneberg; T Menne; EA Nohr; Bert Hofman; André Uitterlinden; CM van Duijin; Fernando Rivadeneira; Johan Jongste; Ralf Valk; M Wjst; R Jogi; F Geller; HA Boyd; JC Murray; C Kim; F Mentch; M March; M Mangino; TD Spector; V Bataille; CE Pennell; PG Holt; P Sly; CMT Tiesler; E Thiering; T Illig; M Imboden; W Nystad; A Simpson; JJ (Jouke Jan) Hottenga; D Postma; GH Koppelman; HA Smit; C Soderhall; B Chawes; E Kreiner-Moller; H Bisgaard; E Melen; DI Boomsma; A Custovic; B Jacobsson; NM Probst-Hensch; LJ Palmer; D Glass; H Hakonarson; M Melbye; DL Jarvis; Vincent Jaddoe; C Gieger; DP Strachan; NG Martin; MR Jarvelin; J (Joachim) Heinrich; DM Evans; S Weidinger

doi:10.1038/ng.1017

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

L Paternoster, M Standl, CM Chen, A Ramasamy, K Bonnelykke, Liesbeth Duijts, MA Ferreira, AC Alves, JP Thyssen, E Albrecht, H Baurecht, BWA Feenstra, PMA Sleiman, P Hysi, NM Warrington, I Curjuric, R Myhre, JA Curtin, MM Groen-Blokhuis, M KerkhofA Saaf, A Franke, D Ellinghaus, R Folster-Holst, E Dermitzakis, SB Montgomery, H Prokisch, K Heim, AL Hartikainen, A Pouta, J Pekkanen, AIF Blakemore, JL Buxton, M Kaakinen, DL Duffy, PA Madden, AC Heath, GW Montgomery, PJ Thompson, MC Matheson, P Le Souef, B St Pourcain, GD Smith, J Henderson, JP Kemp, NJ Timpson, P Deloukas, SM Ring, HE Wichmann, M Muller-Nurasyid, N Novak, N Klopp, E Rodriguez, W McArdle, A Linneberg, T Menne, EA Nohr, Bert Hofman, André Uitterlinden, CM van Duijin, Fernando Rivadeneira, Johan Jongste, Ralf Valk, M Wjst, R Jogi, F Geller, HA Boyd, JC Murray, C Kim, F Mentch, M March, M Mangino, TD Spector, V Bataille, CE Pennell, PG Holt, P Sly, CMT Tiesler, E Thiering, T Illig, M Imboden, W Nystad, A Simpson, JJ (Jouke Jan) Hottenga, D Postma, GH Koppelman, HA Smit, C Soderhall, B Chawes, E Kreiner-Moller, H Bisgaard, E Melen, DI Boomsma, A Custovic, B Jacobsson, NM Probst-Hensch, LJ Palmer, D Glass, H Hakonarson, M Melbye, DL Jarvis, Vincent Jaddoe, C Gieger, DP Strachan, NG Martin, MR Jarvelin, J (Joachim) Heinrich, DM Evans, S Weidinger

Research output: Contribution to journal › Article › Academic › peer-review

298 Citations (Scopus)

Abstract

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 x 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 x 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 x 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 language	Undefined/Unknown
Pages (from-to)	187-192
Number of pages	6
Journal	Nature Genetics
Volume	44
Issue number	2
DOIs	https://doi.org/10.1038/ng.1017
Publication status	Published - 2012

Research programs

EMC MM-01-39-09-A
EMC MM-04-54-08-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC OR-01-54-02

Access to Document

10.1038/ng.1017

http://hdl.handle.net/1765/55487

Cite this

Paternoster, L., Standl, M., Chen, CM., Ramasamy, A., Bonnelykke, K., Duijts, L., Ferreira, MA., Alves, AC., Thyssen, JP., Albrecht, E., Baurecht, H., Feenstra, BWA., Sleiman, PMA., Hysi, P., Warrington, NM., Curjuric, I., Myhre, R., Curtin, JA., Groen-Blokhuis, MM., ... Weidinger, S. (2012). Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nature Genetics, 44(2), 187-192. https://doi.org/10.1038/ng.1017

@article{6e0e8fb0b9db4f4daff9f99be6dfe9fe,

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

abstract = "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 x 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 x 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 x 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.",

author = "L Paternoster and M Standl and CM Chen and A Ramasamy and K Bonnelykke and Liesbeth Duijts and MA Ferreira and AC Alves and JP Thyssen and E Albrecht and H Baurecht and BWA Feenstra and PMA Sleiman and P Hysi and NM Warrington and I Curjuric and R Myhre and JA Curtin and MM Groen-Blokhuis and M Kerkhof and A Saaf and A Franke and D Ellinghaus and R Folster-Holst and E Dermitzakis and SB Montgomery and H Prokisch and K Heim and AL Hartikainen and A Pouta and J Pekkanen and AIF Blakemore and JL Buxton and M Kaakinen and DL Duffy and PA Madden and AC Heath and GW Montgomery and PJ Thompson and MC Matheson and {Le Souef}, P and {St Pourcain}, B and GD Smith and J Henderson and JP Kemp and NJ Timpson and P Deloukas and SM Ring and HE Wichmann and M Muller-Nurasyid and N Novak and N Klopp and E Rodriguez and W McArdle and A Linneberg and T Menne and EA Nohr and Bert Hofman and Andr{\'e} Uitterlinden and {van Duijin}, CM and Fernando Rivadeneira and Johan Jongste and Ralf Valk and M Wjst and R Jogi and F Geller and HA Boyd and JC Murray and C Kim and F Mentch and M March and M Mangino and TD Spector and V Bataille and CE Pennell and PG Holt and P Sly and CMT Tiesler and E Thiering and T Illig and M Imboden and W Nystad and A Simpson and Hottenga, {JJ (Jouke Jan)} and D Postma and GH Koppelman and HA Smit and C Soderhall and B Chawes and E Kreiner-Moller and H Bisgaard and E Melen and DI Boomsma and A Custovic and B Jacobsson and NM Probst-Hensch and LJ Palmer and D Glass and H Hakonarson and M Melbye and DL Jarvis and Vincent Jaddoe and C Gieger and DP Strachan and NG Martin and MR Jarvelin and Heinrich, {J (Joachim)} and DM Evans and S Weidinger",

year = "2012",

doi = "10.1038/ng.1017",

language = "Undefined/Unknown",

volume = "44",

pages = "187--192",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "2",

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Paternoster, L, Standl, M, Chen, CM, Ramasamy, A, Bonnelykke, K, Duijts, L, Ferreira, MA, Alves, AC, Thyssen, JP, Albrecht, E, Baurecht, H, Feenstra, BWA, Sleiman, PMA, Hysi, P, Warrington, NM, Curjuric, I, Myhre, R, Curtin, JA, Groen-Blokhuis, MM, Kerkhof, M, Saaf, A, Franke, A, Ellinghaus, D, Folster-Holst, R, Dermitzakis, E, Montgomery, SB, Prokisch, H, Heim, K, Hartikainen, AL, Pouta, A, Pekkanen, J, Blakemore, AIF, Buxton, JL, Kaakinen, M, Duffy, DL, Madden, PA, Heath, AC, Montgomery, GW, Thompson, PJ, Matheson, MC, Le Souef, P, St Pourcain, B, Smith, GD, Henderson, J, Kemp, JP, Timpson, NJ, Deloukas, P, Ring, SM, Wichmann, HE, Muller-Nurasyid, M, Novak, N, Klopp, N, Rodriguez, E, McArdle, W, Linneberg, A, Menne, T, Nohr, EA, Hofman, B , Uitterlinden, A, van Duijin, CM, Rivadeneira, F, Jongste, J, Valk, R, Wjst, M, Jogi, R, Geller, F, Boyd, HA, Murray, JC, Kim, C, Mentch, F, March, M, Mangino, M, Spector, TD, Bataille, V, Pennell, CE, Holt, PG, Sly, P, Tiesler, CMT, Thiering, E, Illig, T, Imboden, M, Nystad, W, Simpson, A, Hottenga, JJ, Postma, D, Koppelman, GH, Smit, HA, Soderhall, C, Chawes, B, Kreiner-Moller, E, Bisgaard, H, Melen, E, Boomsma, DI, Custovic, A, Jacobsson, B, Probst-Hensch, NM, Palmer, LJ, Glass, D, Hakonarson, H, Melbye, M, Jarvis, DL, Jaddoe, V, Gieger, C, Strachan, DP, Martin, NG, Jarvelin, MR, Heinrich, J, Evans, DM & Weidinger, S 2012, 'Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis', Nature Genetics, vol. 44, no. 2, pp. 187-192. https://doi.org/10.1038/ng.1017

TY - JOUR

T1 - Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

AU - Paternoster, L

AU - Standl, M

AU - Chen, CM

AU - Ramasamy, A

AU - Bonnelykke, K

AU - Duijts, Liesbeth

AU - Ferreira, MA

AU - Alves, AC

AU - Thyssen, JP

AU - Albrecht, E

AU - Baurecht, H

AU - Feenstra, BWA

AU - Sleiman, PMA

AU - Hysi, P

AU - Warrington, NM

AU - Curjuric, I

AU - Myhre, R

AU - Curtin, JA

AU - Groen-Blokhuis, MM

AU - Kerkhof, M

AU - Saaf, A

AU - Franke, A

AU - Ellinghaus, D

AU - Folster-Holst, R

AU - Dermitzakis, E

AU - Montgomery, SB

AU - Prokisch, H

AU - Heim, K

AU - Hartikainen, AL

AU - Pouta, A

AU - Pekkanen, J

AU - Blakemore, AIF

AU - Buxton, JL

AU - Kaakinen, M

AU - Duffy, DL

AU - Madden, PA

AU - Heath, AC

AU - Montgomery, GW

AU - Thompson, PJ

AU - Matheson, MC

AU - Le Souef, P

AU - St Pourcain, B

AU - Smith, GD

AU - Henderson, J

AU - Kemp, JP

AU - Timpson, NJ

AU - Deloukas, P

AU - Ring, SM

AU - Wichmann, HE

AU - Muller-Nurasyid, M

AU - Novak, N

AU - Klopp, N

AU - Rodriguez, E

AU - McArdle, W

AU - Linneberg, A

AU - Menne, T

AU - Nohr, EA

AU - Hofman, Bert

AU - Uitterlinden, André

AU - van Duijin, CM

AU - Rivadeneira, Fernando

AU - Jongste, Johan

AU - Valk, Ralf

AU - Wjst, M

AU - Jogi, R

AU - Geller, F

AU - Boyd, HA

AU - Murray, JC

AU - Kim, C

AU - Mentch, F

AU - March, M

AU - Mangino, M

AU - Spector, TD

AU - Bataille, V

AU - Pennell, CE

AU - Holt, PG

AU - Sly, P

AU - Tiesler, CMT

AU - Thiering, E

AU - Illig, T

AU - Imboden, M

AU - Nystad, W

AU - Simpson, A

AU - Hottenga, JJ (Jouke Jan)

AU - Postma, D

AU - Koppelman, GH

AU - Smit, HA

AU - Soderhall, C

AU - Chawes, B

AU - Kreiner-Moller, E

AU - Bisgaard, H

AU - Melen, E

AU - Boomsma, DI

AU - Custovic, A

AU - Jacobsson, B

AU - Probst-Hensch, NM

AU - Palmer, LJ

AU - Glass, D

AU - Hakonarson, H

AU - Melbye, M

AU - Jarvis, DL

AU - Jaddoe, Vincent

AU - Gieger, C

AU - Strachan, DP

AU - Martin, NG

AU - Jarvelin, MR

AU - Heinrich, J (Joachim)

AU - Evans, DM

AU - Weidinger, S

PY - 2012

Y1 - 2012

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 x 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 x 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 x 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 x 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 x 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 x 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

C2 - 22197932

SN - 1061-4036

VL - 44

SP - 187

EP - 192

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -