title: A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer.
abstract: In Western countries, prostate cancer is the most prevalent cancer of men and one of the leading causes of cancer-related death in men. Several genome-wide association studies have yielded numerous common variants conferring risk of prostate cancer. Here, we analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders. We identified a new low-frequency variant at 8q24 associated with prostate cancer in European populations, rs188140481[A] (odds ratio (OR) = 2.90; P(combined) = 6.2 × 10(-34)), with an average risk allele frequency in controls of 0.54%. This variant is only very weakly correlated (r(2) ≤ 0.06) with previously reported risk variants at 8q24, and its association remains significant after adjustment for all known risk-associated variants. Carriers of rs188140481[A] were diagnosed with prostate cancer 1.26 years younger than non-carriers (P = 0.0059). We also report results for a previously described HOXB13 variant (rs138213197[T]), confirming it as a prostate cancer risk variant in populations from across Europe.
authors.affiliation: deCODE genetics, Reykjavik, Iceland. julius@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: Gisli
authors.initials: G
authors.lastname: Masson
authors.forename: Bjarni A
authors.initials: BA
authors.lastname: Agnarsson
authors.forename: Kristrun R
authors.initials: KR
authors.lastname: Benediktsdottir
authors.forename: Asgeir
authors.initials: A
authors.lastname: Sigurdsson
authors.forename: Olafur Th
authors.initials: OT
authors.lastname: Magnusson
authors.forename: Sigurjon A
authors.initials: SA
authors.lastname: Gudjonsson
authors.forename: Droplaug N
authors.initials: DN
authors.lastname: Magnusdottir
authors.forename: Hrefna
authors.initials: H
authors.lastname: Johannsdottir
authors.forename: Hafdis Th
authors.initials: HT
authors.lastname: Helgadottir
authors.forename: Simon N
authors.initials: SN
authors.lastname: Stacey
authors.forename: Adalbjorg
authors.initials: A
authors.lastname: Jonasdottir
authors.forename: Stefania B
authors.initials: SB
authors.lastname: Olafsdottir
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Jon G
authors.initials: JG
authors.lastname: Jonasson
authors.forename: Laufey
authors.initials: L
authors.lastname: Tryggvadottir
authors.forename: Sebastian
authors.initials: S
authors.lastname: Navarrete
authors.forename: Fernando
authors.initials: F
authors.lastname: Fuertes
authors.forename: Brian T
authors.initials: BT
authors.lastname: Helfand
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Hu
authors.forename: Irma E
authors.initials: IE
authors.lastname: Csiki
authors.forename: Ioan N
authors.initials: IN
authors.lastname: Mates
authors.forename: Viorel
authors.initials: V
authors.lastname: Jinga
authors.forename: Katja K H
authors.initials: KK
authors.lastname: Aben
authors.forename: Inge M
authors.initials: IM
authors.lastname: van Oort
authors.forename: Sita H
authors.initials: SH
authors.lastname: Vermeulen
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.forename: Freddy C
authors.initials: FC
authors.lastname: Hamdy
authors.forename: Chi-Fai
authors.initials: CF
authors.lastname: Ng
authors.forename: Peter K F
authors.initials: PK
authors.lastname: Chiu
authors.forename: Kin-Mang
authors.initials: KM
authors.lastname: Lau
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: Jose I
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: Gudmundur V
authors.initials: GV
authors.lastname: Einarsson
authors.forename: Rosa B
authors.initials: RB
authors.lastname: Barkardottir
authors.forename: Eirikur
authors.initials: E
authors.lastname: Jonsson
authors.forename: Dana
authors.initials: D
authors.lastname: Mates
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
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: D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002460:Cell Line; D002898:Chromosomes, Human, Pair 8; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007055:Iceland; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins