Genome-Wide Meta-Analysis Implicates Mediators of Hair Follicle Development and Morphogenesis in Risk for Severe Acne

November 2018 in “ Nature Communications ”

Christos Petridis, Alexander A. Navarini, Nick Dand, Jake Saklatvala, David Baudry, Michael Duckworth, Michael H. Allen, Charles Curtis, Susan J. Lee, A. David Burden, Alison Layton, Véronique Bataille, Andrew Pink, A.B. Alexandroff, Alex Anstey, J. Azad, Omar Aziz, Nigel Burrows, Aamir Butt, P. Cartwright, Anna Chapman, Timothy Clayton, S. Cliff, T.P. Cutler, B. M. Daly, A. Darvay, Claudia DeGiovanni, Anthony M. Downs, Colm Dwyer, John English, Adam Ferguson, Colin Fleming, Elisabeth A. Fraser-Andrews, Mark Goodfield, Clive Grattan, H C Hempel, Sue Hood, B.R. HUGHES, Evmorfia Ladoyanni, Calum C. Lyon, Ali Mahmud, Moshin Malik, Eleanor Mallon, Simon Meggitt, Andrew G. Messenger, Yaaseen Moosa, S.E. Munn, Anthony D. Ormerod, Deepak Rallan, Janet Ross, Ingrid Salvary, Rachel Wachsmuth, Shyamal Wahie, Shernaz Walton, Sarah Walsh, Diane Williamson, Carolyn Willis, Isabelle Carlavan, Johannes J. Voegel, Tim D. Spector, Richard C. Trembath, John A. McGrath, Catherine Smith, Jonathan Barker, Michael A. Simpson

WNT10A SEMA4B LAMC2 epidermolysis bullosa pilosebaceous unit genetic variations skin structure hair follicle development morphogenesis

TLDR Genetic variations affecting skin structure play a key role in severe acne.

A genome-wide association study involving 3,823 acne cases and 16,144 controls, followed by a meta-analysis with previous data, identified 20 independent association signals at 15 risk loci, 12 of which were novel. The study implicated variants in WNT10A and SEMA4B, and found that risk alleles at the 1q25 locus increased LAMC2 expression, linked to epidermolysis bullosa. These results suggested that genetic variations affecting skin structure and maintenance, particularly the pilosebaceous unit, played a crucial role in severe acne predisposition.