TY - JOUR
T1 - Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne
AU - The Acne Genetic Study Group
AU - Petridis, Christos
AU - Navarini, Alexander A.
AU - Dand, Nick
AU - Saklatvala, Jake
AU - Baudry, David
AU - Duckworth, Michael
AU - Allen, Michael H.
AU - Curtis, Charles J.
AU - Lee, Sang Hyuck
AU - Burden, A. David
AU - Layton, Alison
AU - Bataille, Veronique
AU - Pink, Andrew E.
AU - Alexandroff, Anton
AU - Anstey, Alex
AU - Azad, Jaskiran
AU - Aziz, Omar
AU - Burrows, Nigel
AU - Butt, Aamir
AU - Cartwright, Peter
AU - Chapman, Anna
AU - Clayton, Timothy H.
AU - Cliff, Sandeep
AU - Cutler, Tim
AU - Daly, Brigid
AU - Darvay, Amrit
AU - DeGiovanni, Claudia
AU - Downs, Anthony
AU - Dwyer, Colm
AU - English, John
AU - Ferguson, Adam
AU - Fleming, Colin
AU - Fraser-Andrews, Elizabeth
AU - Goodfield, Mark
AU - Grattan, Clive E.
AU - Hempel, Hartmut
AU - Hood, Sue
AU - Hughes, Bronwyn
AU - Ladoyanni, Evmorfia
AU - Lyon, Calum
AU - Mahmud, Ali
AU - Malik, Moshin
AU - Mallon, Eleanor
AU - Meggitt, Simon
AU - Messenger, Andrew
AU - Moosa, Yaaseen
AU - Munn, Stephanie
AU - Ormerod, Anthony
AU - Rallan, Deepak
AU - Ross, Janet
AU - McGrath, John Alexander
AU - Barker, Jonathan Nicholas William Noel
AU - Smith, Catherine H
AU - Spector, Timothy D.
AU - Barker, Jonathan N.
AU - Simpson, Michael A.
PY - 2018/12/12
Y1 - 2018/12/12
N2 - Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne.
AB - Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne.
UR - http://www.scopus.com/inward/record.url?scp=85058572472&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-07459-5
DO - 10.1038/s41467-018-07459-5
M3 - Article
C2 - 30542056
AN - SCOPUS:85058572472
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5075
ER -