Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma

• Published in: Human molecular genetics Vol. 23; no. 11; pp. 3045 - 3053
• Main Authors: Stacey, Simon N., Sulem, Patrick, Gudbjartsson, Daniel F., Jonasdottir, Aslaug, Thorleifsson, Gudmar, Gudjonsson, Sigurjon A., Masson, Gisli, Gudmundsson, Julius, Sigurgeirsson, Bardur, Benediktsdottir, Kristrun R., Thorisdottir, Kristin, Ragnarsson, Rafn, Fuentelsaz, Victoria, Corredera, Cristina, Grasa, Matilde, Planelles, Dolores, Sanmartin, Onofre, Rudnai, Peter, Gurzau, Eugene, Koppova, Kvetoslava, Hemminki, Kari, Nexø, Bjørn A, Tjønneland, Anne, Overvad, Kim, Johannsdottir, Hrefna, Helgadottir, Hafdis T., Thorsteinsdottir, Unnur, Kong, Augustine, Vogel, Ulla, Kumar, Rajiv, Nagore, Eduardo, Mayordomo, José I., Rafnar, Thorunn, Olafsson, Jon H., Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2014
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Surface - genetics; Association Studies; Carcinoma, Basal Cell - genetics; Child; Female; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Genotype; Germ Cells - metabolism; Germ-Line Mutation; GTP-Binding Protein Regulators - genetics; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Skin Neoplasms - genetics; Transglutaminases - genetics; Young Adult
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddt671

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide association study of 38.5 million single nucleotide polymorphisms (SNPs) and small indels identified through whole-genome sequencing of 2230 Icelanders. We imputed genotypes for 4208 BCC patients and 109 408 controls using Illumina SNP chip typing data, carried out association tests and replicated the findings in independent population samples. We found new BCC susceptibility loci at TGM3 (rs214782[G], P = 5.5 × 10−17, OR = 1.29) and RGS22 (rs7006527[C], P = 8.7 × 10−13, OR = 0.77). TGM3 encodes transglutaminase type 3, which plays a key role in production of the cornified envelope during epidermal differentiation.