title: Discovery of common variants associated with low TSH levels and thyroid cancer risk.
abstract: To search for sequence variants conferring risk of nonmedullary thyroid cancer, we focused our analysis on 22 SNPs with a P < 5 × 10(-8) in a genome-wide association study on levels of thyroid stimulating hormone (TSH) in 27,758 Icelanders. Of those, rs965513 has previously been shown to associate with thyroid cancer. The remaining 21 SNPs were genotyped in 561 Icelandic individuals with thyroid cancer (cases) and up to 40,013 controls. Variants suggestively associated with thyroid cancer (P < 0.05) were genotyped in an additional 595 non-Icelandic cases and 2,604 controls. After combining the results, three variants were shown to associate with thyroid cancer: rs966423 on 2q35 (OR = 1.34; P(combined) = 1.3 × 10(-9)), rs2439302 on 8p12 (OR = 1.36; P(combined) = 2.0 × 10(-9)) and rs116909374 on 14q13.3 (OR = 2.09; P(combined) = 4.6 × 10(-11)), a region previously reported to contain an uncorrelated variant conferring risk of thyroid cancer. A strong association (P = 9.1 × 10(-91)) was observed between rs2439302 on 8p12 and expression of NRG1, which encodes the signaling protein neuregulin 1, in blood.
authors.affiliation: deCODE Genetics, Reykjavik, Iceland. julius.gudmundsson@decode.is
authors.forename: Julius
authors.initials: J
authors.lastname: Gudmundsson
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Jon G
authors.initials: JG
authors.lastname: Jonasson
authors.forename: Gisli
authors.initials: G
authors.lastname: Masson
authors.forename: Huiling
authors.initials: H
authors.lastname: He
authors.forename: Aslaug
authors.initials: A
authors.lastname: Jonasdottir
authors.forename: Asgeir
authors.initials: A
authors.lastname: Sigurdsson
authors.forename: Simon N
authors.initials: SN
authors.lastname: Stacey
authors.forename: Hrefna
authors.initials: H
authors.lastname: Johannsdottir
authors.forename: Hafdis Th
authors.initials: HT
authors.lastname: Helgadottir
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nagy
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Ringel
authors.forename: Richard T
authors.initials: RT
authors.lastname: Kloos
authors.forename: Marieke C H
authors.initials: MC
authors.lastname: de Visser
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Esperanza
authors.initials: E
authors.lastname: Aguillo
authors.forename: Angeles
authors.initials: A
authors.lastname: Panadero
authors.forename: Enrique
authors.initials: E
authors.lastname: Prats
authors.forename: Almudena
authors.initials: A
authors.lastname: Garcia-Castaño
authors.forename: Ana
authors.initials: A
authors.lastname: De Juan
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.forename: G Bragi
authors.initials: GB
authors.lastname: Walters
authors.forename: Hjordis
authors.initials: H
authors.lastname: Bjarnason
authors.forename: Laufey
authors.initials: L
authors.lastname: Tryggvadottir
authors.forename: Gudmundur I
authors.initials: GI
authors.lastname: Eyjolfsson
authors.forename: Unnur S
authors.initials: US
authors.lastname: Bjornsdottir
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.forename: Isleifur
authors.initials: I
authors.lastname: Olafsson
authors.forename: Kristleifur
authors.initials: K
authors.lastname: Kristjansson
authors.forename: Hoskuldur
authors.initials: H
authors.lastname: Kristvinsson
authors.forename: Olafur T
authors.initials: OT
authors.lastname: Magnusson
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Lambertus A L M
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Thorvaldur
authors.initials: T
authors.lastname: Jonsson
authors.forename: Hannes
authors.initials: H
authors.lastname: Hjartarson
authors.forename: Jose I
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: Romana T
authors.initials: RT
authors.lastname: Netea-Maier
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: Jon
authors.initials: J
authors.lastname: Hrafnkelsson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007055:Iceland; D020890:Neuregulin-1 / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*; D013972:Thyrotropin / Q000378:metabolism*
chemical_list: C094131:NRG1 protein, human; D020890:Neuregulin-1; D013972:Thyrotropin