%0 Journal Article
%A Nicoletti, Paola
%A Barrett, Sarah
%A McEvoy, Laurence
%A Daly, Ann K
%A Aithal, Guruprasad
%A Lucena, M Isabel
%A Andrade, Raul J
%A Wadelius, Mia
%A Hallberg, Pär
%A Stephens, Camilla
%A Bjornsson, Einar S
%A Friedmann, Peter
%A Kainu, Kati
%A Laitinen, Tarja
%A Marson, Anthony
%A Molokhia, Mariam
%A Phillips, Elizabeth
%A Pichler, Werner
%A Romano, Antonino
%A Shear, Neil
%A Sills, Graeme
%A Tanno, Luciana K
%A Swale, Ashley
%A Floratos, Aris
%A Shen, Yufeng
%A Nelson, Matthew R
%A Watkins, Paul B
%A Daly, Mark J
%A Morris, Andrew P
%A Alfirevic, Ana
%A Pirmohamed, Munir
%T Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.
%D 2019
%U http://hdl.handle.net/10668/13926
%X Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR) = 8.0; 95% CI 4.10-15.80; P = 1.2 × 10-9 ) and CBZ-DILI (OR = 7.3; 95% CI 2.47-23.67; P = 0.0004) in European populations. The association with HLA-A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR = 12.9; P = 2.1 × 10-9 ) rather than by Stevens-Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA-B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation.
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