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16 results on '"Benediktsdottir, K.R."'

1. CDKN2A mutations and melanoma risk in the Icelandic population

Author

Goldstein, A.M., Stacey, S.N., Olafsson, J.H., Jonsson, G.F., Helgason, A., Sulem, P., Sigurgeirsson, B., Benediktsdottir, K.R., Thorisdottir, K., Ragnarsson, R., Kjartansson, J., Kostic, J., Masson, G., Kristjansson, K., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., Rafnar, T., Tucker, M.A., and Stefansson, K.

Subjects
Melanoma -- Risk factors, Melanoma -- Genetic aspects, Melanoma -- Demographic aspects, Melanoma -- Research, Gene mutations -- Research, Health
Published
2008

2. Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer

Author

Stacey, S.N., Kehr, B., Gudmundsson, J., Zink, F., Jonasdottir, A., Gudjonsson, S.A., Sigurdsson, A., Halldorsson, B.V., Agnarsson, B.A., Benediktsdottir, K.R., Aben, K.K.H., Vermeulen, S.H., Cremers, R.G., Panadero, A., Helfand, B.T., Cooper, P.R., Donovan, J.L., Hamdy, F.C., Jinga, V., Okamoto, I., Jonasson, J.G., Tryggvadottir, L., Johannsdottir, H., Kristinsdottir, A.M., Masson, G., Magnusson, O.T., Iordache, P.D., Helgason, A., Helgason, H., Sulem, P., Gudbjartsson, D.F., Kong, A., Jonsson, E., Barkardottir, R.B., Einarsson, G.V., Rafnar, T., Thorsteinsdottir, U., Mates, I.N., Neal, D.E., Catalona, W.J., Mayordomo, J.I., Kiemeney, L.A., Thorleifsson, G., Stefansson, K., Stacey, S.N., Kehr, B., Gudmundsson, J., Zink, F., Jonasdottir, A., Gudjonsson, S.A., Sigurdsson, A., Halldorsson, B.V., Agnarsson, B.A., Benediktsdottir, K.R., Aben, K.K.H., Vermeulen, S.H., Cremers, R.G., Panadero, A., Helfand, B.T., Cooper, P.R., Donovan, J.L., Hamdy, F.C., Jinga, V., Okamoto, I., Jonasson, J.G., Tryggvadottir, L., Johannsdottir, H., Kristinsdottir, A.M., Masson, G., Magnusson, O.T., Iordache, P.D., Helgason, A., Helgason, H., Sulem, P., Gudbjartsson, D.F., Kong, A., Jonsson, E., Barkardottir, R.B., Einarsson, G.V., Rafnar, T., Thorsteinsdottir, U., Mates, I.N., Neal, D.E., Catalona, W.J., Mayordomo, J.I., Kiemeney, L.A., Thorleifsson, G., and Stefansson, K.

Abstract

Contains fulltext : 172827.pdf (publisher's version ) (Open Access), Transcriptional and splicing anomalies have been observed in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell carcinoma (BCC) and linked to a germline SNP rs700635. Here, we show that the rs700635[C] allele, which is associated with increased risk of BCC and breast cancer, is protective against prostate cancer [odds ratio (OR) = 0.91, P = 1.0 x 10(-6)]. rs700635[C] is also associated with failures to correctly splice out CASP8 intron 8 in breast and prostate tumours and in corresponding normal tissues. Investigation of rs700635[C] carriers revealed that they have a human-specific short interspersed element-variable number of tandem repeat-Alu (SINE-VNTR-Alu), subfamily-E retrotransposon (SVA-E) inserted into CASP8 intron 8. The SVA-E shows evidence of prior activity, because it has transduced some CASP8 sequences during subsequent retrotransposition events. Whole-genome sequence (WGS) data were used to tag the SVA-E with a surrogate SNP rs1035142[T] (r(2) = 0.999), which showed associations with both the splicing anomalies (P = 6.5 x 10(-32)) and with protection against prostate cancer (OR = 0.91, P = 3.8 x 10(-7)).

Published
2016

3. A variant in FTO shows association with melanoma risk not due to BMI

Author

Iles, M.M., Law, M.H., Stacey, S.N., Han, J., Fang, S., Pfeiffer, R., Harland, M., MacGregor, S., Taylor, J.C., Aben, K.K.H., Akslen, L.A., Avril, M.F., Azizi, E., Bakker, B., Benediktsdottir, K.R., Bergman, W., Scarra, G.B., Brown, K.M., Calista, D., Chaudru, V., Fargnoli, M.C., Cust, A.E., Demenais, F., Waal, A.C. de, Debniak, T., Elder, D.E., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E.M., Goldstein, A.M., Gruis, N.A., Hansson, J., Helsing, P., Hocevar, M., Hoiom, V., Hopper, J.L., Ingvar, C., Janssen, M., Jenkins, M.A., Kanetsky, P.A., Kiemeney, L.A.L.M., Lang, J., Lathrop, G.M., Leachman, S., Lee, J.E., Lubinski, J., Mackie, R.M., Mann, G.J., Martin, N.G., Mayordomo, J.I., Molven, A., Mulder, S., Nagore, E., Novakovic, S., Okamoto, I., Olafsson, J.H., Olsson, H., Pehamberger, H., Peris, K., Grasa, M.P., Planelles, D., Puig, S., Puig-Butille, J.A., Randerson-Moor, J., Requena, C., Rivoltini, L., Rodolfo, M., Santinami, M., Sigurgeirsson, B., Snowden, H., Song, F., Sulem, P., Thorisdottir, K., Tuominen, R., Belle, P. Van, Stoep, N. van der, Rossum, M.M. van, Wei, Q., Wendt, J., Zelenika, D., Zhang, M., Landi, M.T., Thorleifsson, G., Bishop, D.T., Amos, C.I., Hayward, N.K., Stefansson, K., Bishop, J.A., Barrett, J.H., et al., Iles, M.M., Law, M.H., Stacey, S.N., Han, J., Fang, S., Pfeiffer, R., Harland, M., MacGregor, S., Taylor, J.C., Aben, K.K.H., Akslen, L.A., Avril, M.F., Azizi, E., Bakker, B., Benediktsdottir, K.R., Bergman, W., Scarra, G.B., Brown, K.M., Calista, D., Chaudru, V., Fargnoli, M.C., Cust, A.E., Demenais, F., Waal, A.C. de, Debniak, T., Elder, D.E., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E.M., Goldstein, A.M., Gruis, N.A., Hansson, J., Helsing, P., Hocevar, M., Hoiom, V., Hopper, J.L., Ingvar, C., Janssen, M., Jenkins, M.A., Kanetsky, P.A., Kiemeney, L.A.L.M., Lang, J., Lathrop, G.M., Leachman, S., Lee, J.E., Lubinski, J., Mackie, R.M., Mann, G.J., Martin, N.G., Mayordomo, J.I., Molven, A., Mulder, S., Nagore, E., Novakovic, S., Okamoto, I., Olafsson, J.H., Olsson, H., Pehamberger, H., Peris, K., Grasa, M.P., Planelles, D., Puig, S., Puig-Butille, J.A., Randerson-Moor, J., Requena, C., Rivoltini, L., Rodolfo, M., Santinami, M., Sigurgeirsson, B., Snowden, H., Song, F., Sulem, P., Thorisdottir, K., Tuominen, R., Belle, P. Van, Stoep, N. van der, Rossum, M.M. van, Wei, Q., Wendt, J., Zelenika, D., Zhang, M., Landi, M.T., Thorleifsson, G., Bishop, D.T., Amos, C.I., Hayward, N.K., Stefansson, K., Bishop, J.A., Barrett, J.H., and et al.

Abstract

Contains fulltext : 118658.pdf (publisher's version ) (Closed access), We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanoma-susceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.

Published
2013

4. A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer

Author

Gudmundsson, J., Sulem, P., Gudbjartsson, D.F., Masson, G., Agnarsson, B.A., Benediktsdottir, K.R., Sigurdsson, A., Magnusson, O.T., Gudjonsson, S.A., Magnusdottir, D.N., Johannsdottir, H., Helgadottir, H.T., Stacey, S.N., Jonasdottir, A., Olafsdottir, S.B., Thorleifsson, G., Jonasson, J.G., Tryggvadottir, L., Navarrete, S., Fuertes, F., Helfand, B.T., Hu, Q., Csiki, I.E., Mates, I.N., Jinga, V., Aben, K.K.H., Oort, I.M. van, Vermeulen, S., Donovan, J.L., Hamdy, F.C., Ng, C.F., Chiu, P.K., Lau, K.M., Ng, M.C., Gulcher, J.R., Kong, A., Catalona, W.J., Mayordomo, J.I., Einarsson, G.V., Barkardottir, R.B., Jonsson, E., Mates, D., Neal, D.E., Kiemeney, L.A.L.M., Thorsteinsdottir, U., Rafnar, T., Stefansson, K., Gudmundsson, J., Sulem, P., Gudbjartsson, D.F., Masson, G., Agnarsson, B.A., Benediktsdottir, K.R., Sigurdsson, A., Magnusson, O.T., Gudjonsson, S.A., Magnusdottir, D.N., Johannsdottir, H., Helgadottir, H.T., Stacey, S.N., Jonasdottir, A., Olafsdottir, S.B., Thorleifsson, G., Jonasson, J.G., Tryggvadottir, L., Navarrete, S., Fuertes, F., Helfand, B.T., Hu, Q., Csiki, I.E., Mates, I.N., Jinga, V., Aben, K.K.H., Oort, I.M. van, Vermeulen, S., Donovan, J.L., Hamdy, F.C., Ng, C.F., Chiu, P.K., Lau, K.M., Ng, M.C., Gulcher, J.R., Kong, A., Catalona, W.J., Mayordomo, J.I., Einarsson, G.V., Barkardottir, R.B., Jonsson, E., Mates, D., Neal, D.E., Kiemeney, L.A.L.M., Thorsteinsdottir, U., Rafnar, T., and Stefansson, K.

Abstract

Contains fulltext : 108025.pdf (publisher's version ) (Closed access), 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 x 10(-34)), with an average risk allele frequency in controls of 0.54%. This variant is only very weakly correlated (r(2)

Published
2012

5. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility

Author

Stacey, S.N., Sulem, P., Jonasdottir, A., Masson, G., Gudmundsson, J., Gudbjartsson, D.F., Magnusson, O.T., Gudjonsson, S.A., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Nexo, B.A., Tjonneland, A., Overvad, K., Rudnai, P., Gurzau, E, Koppova, K., Hemminki, K., Corredera, C., Fuentelsaz, V., Grasa, P., Navarrete, S., Fuertes, F., Garcia-Prats, M.D., Sanambrosio, E., Panadero, A., Juan, A. de, Garcia, A., Rivera, F., Planelles, D., Soriano, V., Requena, C., Aben, K.K.H., Rossum, M.M. van, Cremers, R.G.H.M., Oort, I.M. van, Spronsen, D.J. van, Schalken, J.A., Peters, W.H.M., Helfand, B.T., Donovan, J.L., Hamdy, F.C., Badescu, D., Codreanu, O., Jinga, M., Csiki, I.E., Constantinescu, V., Badea, P., Mates, I.N., Dinu, D.E., Constantin, A., Mates, D., Kristjansdottir, S., Agnarsson, B.A., Jonsson, E., Barkardottir, R.B., Einarsson, G.V., Sigurdsson, F., Moller, P.H., Stefansson, T., Valdimarsson, T., Johannsson, O.T., Sigurdsson, H., Jonsson, T., Jonasson, J.G., Tryggvadottir, L., Rice, T., Hansen, H.M., Xiao, Y., Lachance, D.H., Kosel, M.L., Decker, P.A., Thorleifsson, G., Johannsdottir, H., Helgadottir, H.T., Sigurdsson, A., Steinthorsdottir, V., Lindblom, A., Sandler, R.S., Keku, T.O., Banasik, K., Jorgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Jinga, V., Neal, D.E., Catalona, W.J., Wrensch, M., Wiencke, J., Jenkins, R.B., Nagore, E., Vogel, U., Kiemeney, L.A.L.M., Kumar, R., Mayordomo, J.I., Olafsson, J.H., et al., Stacey, S.N., Sulem, P., Jonasdottir, A., Masson, G., Gudmundsson, J., Gudbjartsson, D.F., Magnusson, O.T., Gudjonsson, S.A., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Nexo, B.A., Tjonneland, A., Overvad, K., Rudnai, P., Gurzau, E, Koppova, K., Hemminki, K., Corredera, C., Fuentelsaz, V., Grasa, P., Navarrete, S., Fuertes, F., Garcia-Prats, M.D., Sanambrosio, E., Panadero, A., Juan, A. de, Garcia, A., Rivera, F., Planelles, D., Soriano, V., Requena, C., Aben, K.K.H., Rossum, M.M. van, Cremers, R.G.H.M., Oort, I.M. van, Spronsen, D.J. van, Schalken, J.A., Peters, W.H.M., Helfand, B.T., Donovan, J.L., Hamdy, F.C., Badescu, D., Codreanu, O., Jinga, M., Csiki, I.E., Constantinescu, V., Badea, P., Mates, I.N., Dinu, D.E., Constantin, A., Mates, D., Kristjansdottir, S., Agnarsson, B.A., Jonsson, E., Barkardottir, R.B., Einarsson, G.V., Sigurdsson, F., Moller, P.H., Stefansson, T., Valdimarsson, T., Johannsson, O.T., Sigurdsson, H., Jonsson, T., Jonasson, J.G., Tryggvadottir, L., Rice, T., Hansen, H.M., Xiao, Y., Lachance, D.H., Kosel, M.L., Decker, P.A., Thorleifsson, G., Johannsdottir, H., Helgadottir, H.T., Sigurdsson, A., Steinthorsdottir, V., Lindblom, A., Sandler, R.S., Keku, T.O., Banasik, K., Jorgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Jinga, V., Neal, D.E., Catalona, W.J., Wrensch, M., Wiencke, J., Jenkins, R.B., Nagore, E., Vogel, U., Kiemeney, L.A.L.M., Kumar, R., Mayordomo, J.I., Olafsson, J.H., and et al.

Abstract

Contains fulltext : 97569.pdf (publisher's version ) (Closed access), To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 x 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 x 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 x 10(-6)), glioma (OR = 2.35, P = 1.0 x 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 x 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).

Published
2011

6. Mutations in BRIP1 confer high risk of ovarian cancer

Author

Rafnar, T., Gudbjartsson, D.F., Sulem, P., Jonasdottir, A., Sigurdsson, A., Besenbacher, S., Lundin, P., Stacey, S.N., Gudmundsson, J., Magnusson, O.T., Roux, L. le, Orlygsdottir, G., Helgadottir, H.T., Johannsdottir, H., Gylfason, A, Tryggvadottir, L., Jonasson, J.G., Juan, A. de, Ortega, E., Ramon-Cajal, J.M., Garcia-Prats, M.D., Mayordomo, C., Panadero, A., Rivera, F., Aben, K.K.H., Altena, A.M. van, Massuger, L.F.A.G., Aavikko, M., Kujala, P.M., Staff, S., Aaltonen, L.A., Olafsdottir, K., Bjornsson, J., Kong, A., Salvarsdottir, A., Saemundsson, H., Olafsson, K., Benediktsdottir, K.R., Gulcher, J., Masson, G., Kiemeney, L.A.L.M., Mayordomo, J.I., Thorsteinsdottir, U., Stefansson, K., Rafnar, T., Gudbjartsson, D.F., Sulem, P., Jonasdottir, A., Sigurdsson, A., Besenbacher, S., Lundin, P., Stacey, S.N., Gudmundsson, J., Magnusson, O.T., Roux, L. le, Orlygsdottir, G., Helgadottir, H.T., Johannsdottir, H., Gylfason, A, Tryggvadottir, L., Jonasson, J.G., Juan, A. de, Ortega, E., Ramon-Cajal, J.M., Garcia-Prats, M.D., Mayordomo, C., Panadero, A., Rivera, F., Aben, K.K.H., Altena, A.M. van, Massuger, L.F.A.G., Aavikko, M., Kujala, P.M., Staff, S., Aaltonen, L.A., Olafsdottir, K., Bjornsson, J., Kong, A., Salvarsdottir, A., Saemundsson, H., Olafsson, K., Benediktsdottir, K.R., Gulcher, J., Masson, G., Kiemeney, L.A.L.M., Mayordomo, J.I., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 98125.pdf (publisher's version ) (Closed access), Ovarian cancer causes more deaths than any other gynecologic malignancy in developed countries. Sixteen million sequence variants, identified through whole-genome sequencing of 457 Icelanders, were imputed to 41,675 Icelanders genotyped using SNP chips, as well as to their relatives. Sequence variants were tested for association with ovarian cancer (N of affected individuals = 656). We discovered a rare (0.41% allelic frequency) frameshift mutation, c.2040_2041insTT, in the BRIP1 (FANCJ) gene that confers an increase in ovarian cancer risk (odds ratio (OR) = 8.13, P = 2.8 x 10(-14)). The mutation was also associated with increased risk of cancer in general and reduced lifespan by 3.6 years. In a Spanish population, another frameshift mutation in BRIP1, c.1702_1703del, was seen in 2 out of 144 subjects with ovarian cancer and 1 out of 1,780 control subjects (P = 0.016). This allele was also associated with breast cancer (seen in 6/927 cases; P = 0.0079). Ovarian tumors from heterozygous carriers of the Icelandic mutation show loss of the wild-type allele, indicating that BRIP1 behaves like a classical tumor suppressor gene in ovarian cancer.

Published
2011

7. Genetic correction of PSA values using sequence variants associated with PSA levels.

Author

Gudmundsson, J., Besenbacher, S., Sulem, P., Gudbjartsson, D.F., Olafsson, I., Arinbjarnarson, S., Agnarsson, B.A., Benediktsdottir, K.R., Isaksson, H.J., Kostic, J.P., Gudjonsson, S.A., Stacey, S.N., Gylfason, A, Sigurdsson, A., Holm, H., Bjornsdottir, U.S., Eyjolfsson, G.I., Navarrete, S., Fuertes, F., Garcia-Prats, M.D., Polo, E., Checherita, I.A., Jinga, M., Badea, P., Aben, K.K.H., Schalken, J.A., Oort, I.M. van, Sweep, C.G.J., Helfand, B.T., Davis, M., Donovan, J.L., Hamdy, F.C., Kristjansson, K., Gulcher, J.R., Masson, G., Kong, A., Catalona, W.J., Mayordomo, J.I., Geirsson, G., Einarsson, G.V., Barkardottir, R.B., Jonsson, E., Jinga, V., Mates, D., Kiemeney, L.A.L.M., Neal, D.E., Thorsteinsdottir, U., Rafnar, T., Stefansson, K., Gudmundsson, J., Besenbacher, S., Sulem, P., Gudbjartsson, D.F., Olafsson, I., Arinbjarnarson, S., Agnarsson, B.A., Benediktsdottir, K.R., Isaksson, H.J., Kostic, J.P., Gudjonsson, S.A., Stacey, S.N., Gylfason, A, Sigurdsson, A., Holm, H., Bjornsdottir, U.S., Eyjolfsson, G.I., Navarrete, S., Fuertes, F., Garcia-Prats, M.D., Polo, E., Checherita, I.A., Jinga, M., Badea, P., Aben, K.K.H., Schalken, J.A., Oort, I.M. van, Sweep, C.G.J., Helfand, B.T., Davis, M., Donovan, J.L., Hamdy, F.C., Kristjansson, K., Gulcher, J.R., Masson, G., Kong, A., Catalona, W.J., Mayordomo, J.I., Geirsson, G., Einarsson, G.V., Barkardottir, R.B., Jonsson, E., Jinga, V., Mates, D., Kiemeney, L.A.L.M., Neal, D.E., Thorsteinsdottir, U., Rafnar, T., and Stefansson, K.

Abstract

Item does not contain fulltext, Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 x 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.

Published
2010

8. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility.

Author

Gudmundsson, J., Sulem, P., Gudbjartsson, D.F., Blondal, T., Gylfason, A, Agnarsson, B.A., Benediktsdottir, K.R., Magnusdottir, D.N., Orlygsdottir, G., Jakobsdottir, M., Stacey, S.N., Sigurdsson, A., Wahlfors, T., Tammela, T., Breyer, J.P., McReynolds, K.M., Bradley, K.M., Saez, B., Godino, J., Navarrete, S., Fuertes, F., Murillo, L., Polo, E., Aben, K.K.H., Oort, I.M. van, Suarez, B.K., Helfand, B.T., Kan, D., Zanone, C., Frigge, M.L., Kristjansson, K., Gulcher, J.R., Einarsson, G.V., Jonsson, E., Catalona, W.J., Mayordomo, J.I., Kiemeney, L.A.L.M., Smith, J.R., Schleutker, J., Barkardottir, R.B., Kong, A., Thorsteinsdottir, U., Rafnar, T., Stefansson, K., Gudmundsson, J., Sulem, P., Gudbjartsson, D.F., Blondal, T., Gylfason, A, Agnarsson, B.A., Benediktsdottir, K.R., Magnusdottir, D.N., Orlygsdottir, G., Jakobsdottir, M., Stacey, S.N., Sigurdsson, A., Wahlfors, T., Tammela, T., Breyer, J.P., McReynolds, K.M., Bradley, K.M., Saez, B., Godino, J., Navarrete, S., Fuertes, F., Murillo, L., Polo, E., Aben, K.K.H., Oort, I.M. van, Suarez, B.K., Helfand, B.T., Kan, D., Zanone, C., Frigge, M.L., Kristjansson, K., Gulcher, J.R., Einarsson, G.V., Jonsson, E., Catalona, W.J., Mayordomo, J.I., Kiemeney, L.A.L.M., Smith, J.R., Schleutker, J., Barkardottir, R.B., Kong, A., Thorsteinsdottir, U., Rafnar, T., and Stefansson, K.

Abstract

Contains fulltext : 80628.pdf (publisher's version ) (Closed access), We report a prostate cancer genome-wide association follow-on study. We discovered four variants associated with susceptibility to prostate cancer in several European populations: rs10934853[A] (OR = 1.12, P = 2.9 x 10(-10)) on 3q21.3; two moderately correlated (r2 = 0.07) variants, rs16902094[G] (OR = 1.21, P = 6.2 x 10(-15)) and rs445114[T] (OR = 1.14, P = 4.7 x 10(-10)), on 8q24.21; and rs8102476[C] (OR = 1.12, P = 1.6 x 10(-11)) on 19q13.2. We also refined a previous association signal on 11q13 with the SNP rs11228565[A] (OR = 1.23, P = 6.7 x 10(-12)). In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, we estimated that carriers in the top 1.3% of the risk distribution are at a 2.5 times greater risk of developing the disease than members of the general population.

Published
2009

9. New common variants affecting susceptibility to basal cell carcinoma.

Author

Stacey, S.N., Sulem, P., Masson, G., Gudjonsson, S.A., Thorleifsson, G., Jakobsdottir, M., Sigurdsson, A., Gudbjartsson, D.F., Sigurgeirsson, B., Benediktsdottir, K.R., Thorisdottir, K., Ragnarsson, R., Scherer, D., Hemminki, K., Rudnai, P., Gurzau, E, Koppova, K., Botella-Estrada, R., Soriano, V., Juberias, P., Saez, B., Gilaberte, Y., Fuentelsaz, V., Corredera, C., Grasa, M., Hoiom, V., Lindblom, A., Bonenkamp, J.J., Rossum, M.M. van, Aben, K.K.H., Vries, E. de, Santinami, M., Mauro, M.G. Di, Maurichi, A., Wendt, J., Hochleitner, P., Pehamberger, H., Gudmundsson, J., Magnusdottir, D.N., Gretarsdottir, S., Holm, H., Steinthorsdottir, V., Frigge, M.L., Blondal, T., Saemundsdottir, J., Bjarnason, H., Kristjansson, K., Bjornsdottir, G., Okamoto, I., Rivoltini, L., Rodolfo, M., Kiemeney, L.A.L.M., Hansson, J., Nagore, E., Mayordomo, J.I., Kumar, R., Karagas, M.R., Nelson, H.H., Gulcher, J.R., Rafnar, T., Thorsteinsdottir, U., Olafsson, J.H., Kong, A., Stefansson, K., Stacey, S.N., Sulem, P., Masson, G., Gudjonsson, S.A., Thorleifsson, G., Jakobsdottir, M., Sigurdsson, A., Gudbjartsson, D.F., Sigurgeirsson, B., Benediktsdottir, K.R., Thorisdottir, K., Ragnarsson, R., Scherer, D., Hemminki, K., Rudnai, P., Gurzau, E, Koppova, K., Botella-Estrada, R., Soriano, V., Juberias, P., Saez, B., Gilaberte, Y., Fuentelsaz, V., Corredera, C., Grasa, M., Hoiom, V., Lindblom, A., Bonenkamp, J.J., Rossum, M.M. van, Aben, K.K.H., Vries, E. de, Santinami, M., Mauro, M.G. Di, Maurichi, A., Wendt, J., Hochleitner, P., Pehamberger, H., Gudmundsson, J., Magnusdottir, D.N., Gretarsdottir, S., Holm, H., Steinthorsdottir, V., Frigge, M.L., Blondal, T., Saemundsdottir, J., Bjarnason, H., Kristjansson, K., Bjornsdottir, G., Okamoto, I., Rivoltini, L., Rodolfo, M., Kiemeney, L.A.L.M., Hansson, J., Nagore, E., Mayordomo, J.I., Kumar, R., Karagas, M.R., Nelson, H.H., Gulcher, J.R., Rafnar, T., Thorsteinsdottir, U., Olafsson, J.H., Kong, A., and Stefansson, K.

Abstract

Contains fulltext : 81164.pdf (publisher's version ) (Closed access), In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.

Published
2009

10. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.

Author

Rafnar, T., Sulem, P., Stacey, S.N., Geller, F., Gudmundsson, J., Sigurdsson, A., Jakobsdottir, M., Helgadottir, H., Thorlacius, S., Aben, K.K.H., Blondal, T., Thorgeirsson, T.E., Thorleifsson, G., Kristjansson, K., Thorisdottir, K., Ragnarsson, R., Sigurgeirsson, B., Skuladottir, H., Gudbjartsson, T., Isaksson, H.J., Einarsson, G.V., Benediktsdottir, K.R., Agnarsson, B.A., Olafsson, K., Salvarsdottir, A., Bjarnason, H., Asgeirsdottir, M., Kristinsson, K.T., Matthiasdottir, S., Sveinsdottir, S.G., Polidoro, S., Hoiom, V., Botella-Estrada, R., Hemminki, K., Rudnai, P., Bishop, D.T., Campagna, M., Kellen, E., Zeegers, M.P., Verdier, P. de, Ferrer, A., Isla, D., Vidal, M.J., Andres, R., Saez, B., Juberias, P., Banzo, J., Navarrete, S., Tres, A., Kan, D., Lindblom, A., Gurzau, E, Koppova, K., Vegt, F. de, Schalken, J.A., Heijden, H.F.M. van der, Smit, H.J., Termeer, R.A., Oosterwijk, E., Hooij, O. van, Nagore, E., Porru, S., Steineck, G., Hansson, J., Buntinx, F., Catalona, W.J., Matullo, G., Vineis, P., Kiltie, A.E., Mayordomo, J.I., Kumar, R., Kiemeney, L.A.L.M., Frigge, M.L., Jonsson, T., Saemundsson, H., Barkardottir, R.B., Jonsson, E., Jonsson, S., Olafsson, J.H., Gulcher, J.R., Masson, G., Gudbjartsson, D.F., Kong, A., Thorsteinsdottir, U., Stefansson, K., Rafnar, T., Sulem, P., Stacey, S.N., Geller, F., Gudmundsson, J., Sigurdsson, A., Jakobsdottir, M., Helgadottir, H., Thorlacius, S., Aben, K.K.H., Blondal, T., Thorgeirsson, T.E., Thorleifsson, G., Kristjansson, K., Thorisdottir, K., Ragnarsson, R., Sigurgeirsson, B., Skuladottir, H., Gudbjartsson, T., Isaksson, H.J., Einarsson, G.V., Benediktsdottir, K.R., Agnarsson, B.A., Olafsson, K., Salvarsdottir, A., Bjarnason, H., Asgeirsdottir, M., Kristinsson, K.T., Matthiasdottir, S., Sveinsdottir, S.G., Polidoro, S., Hoiom, V., Botella-Estrada, R., Hemminki, K., Rudnai, P., Bishop, D.T., Campagna, M., Kellen, E., Zeegers, M.P., Verdier, P. de, Ferrer, A., Isla, D., Vidal, M.J., Andres, R., Saez, B., Juberias, P., Banzo, J., Navarrete, S., Tres, A., Kan, D., Lindblom, A., Gurzau, E, Koppova, K., Vegt, F. de, Schalken, J.A., Heijden, H.F.M. van der, Smit, H.J., Termeer, R.A., Oosterwijk, E., Hooij, O. van, Nagore, E., Porru, S., Steineck, G., Hansson, J., Buntinx, F., Catalona, W.J., Matullo, G., Vineis, P., Kiltie, A.E., Mayordomo, J.I., Kumar, R., Kiemeney, L.A.L.M., Frigge, M.L., Jonsson, T., Saemundsson, H., Barkardottir, R.B., Jonsson, E., Jonsson, S., Olafsson, J.H., Gulcher, J.R., Masson, G., Gudbjartsson, D.F., Kong, A., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 81560.pdf (publisher's version ) (Closed access), The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

Published
2009

11. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.

Author

Gudbjartsson, D.F., Sulem, P., Stacey, S.N., Goldstein, A.M., Rafnar, T., Sigurgeirsson, B., Benediktsdottir, K.R., Thorisdottir, K., Ragnarsson, R., Sveinsdottir, S.G., Magnusson, V., Lindblom, A., Kostulas, K., Botella-Estrada, R., Soriano, V., Juberias, P., Grasa, M., Saez, B., Andres, R., Scherer, D., Rudnai, P., Gurzau, E, Koppova, K., Kiemeney, L.A.L.M., Jakobsdottir, M., Steinberg, S., Helgason, A., Gretarsdottir, S., Tucker, M.A., Mayordomo, J.I., Nagore, E., Kumar, R., Hansson, J., Olafsson, J.H., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., Stefansson, K., Gudbjartsson, D.F., Sulem, P., Stacey, S.N., Goldstein, A.M., Rafnar, T., Sigurgeirsson, B., Benediktsdottir, K.R., Thorisdottir, K., Ragnarsson, R., Sveinsdottir, S.G., Magnusson, V., Lindblom, A., Kostulas, K., Botella-Estrada, R., Soriano, V., Juberias, P., Grasa, M., Saez, B., Andres, R., Scherer, D., Rudnai, P., Gurzau, E, Koppova, K., Kiemeney, L.A.L.M., Jakobsdottir, M., Steinberg, S., Helgason, A., Gretarsdottir, S., Tucker, M.A., Mayordomo, J.I., Nagore, E., Kumar, R., Hansson, J., Olafsson, J.H., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 69041.pdf (publisher's version ) (Closed access), Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) = 1.45, P = 1.2 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 10(-6)). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.

Published
2008

12. Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer.

Author

Gudmundsson, J., Sulem, P., Rafnar, T., Bergthorsson, J.T., Manolescu, A., Gudbjartsson, D.F., Agnarsson, B.A., Sigurdsson, A., Benediktsdottir, K.R., Blondal, T., Jakobsdottir, M., Stacey, S.N., Kostic, J., Kristinsson, K.T., Birgisdottir, B., Ghosh, S., Magnusdottir, D., Thorlacius, S., Thorleifsson, G., Zheng, S.L., Sun, J., Chang, B.L., Elmore, J.B., Breyer, J.P., McReynolds, K.M., Bradley, K.M., Yaspan, B.L., Wiklund, F., Stattin, P, Lindstrom, S., Adami, H.O., McDonnell, S.K., Schaid, D.J., Cunningham, J.M., Wang, L., Cerhan, J.R., Sauver, J.L. St, Isaacs, S.D., Wiley, K.E., Partin, A.W., Walsh, P.C., Polo, S., Ruiz-Echarri, M., Navarrete, S., Fuertes, F., Saez, B., Godino, J., Weijerman, P.C., Swinkels, D.W., Aben, K.K.H., Witjes, J.A., Suarez, B.K., Helfand, B.T., Frigge, M.L., Kristjansson, K., Ober, C., Jonsson, E., Einarsson, G.V., Xu, J., Gronberg, H., Smith, J.R., Thibodeau, S.N., Isaacs, W.B., Catalona, W.J., Mayordomo, J.I., Kiemeney, L.A.L.M., Barkardottir, R.B., Gulcher, J.R., Thorsteinsdottir, U., Kong, A., Stefansson, K., Gudmundsson, J., Sulem, P., Rafnar, T., Bergthorsson, J.T., Manolescu, A., Gudbjartsson, D.F., Agnarsson, B.A., Sigurdsson, A., Benediktsdottir, K.R., Blondal, T., Jakobsdottir, M., Stacey, S.N., Kostic, J., Kristinsson, K.T., Birgisdottir, B., Ghosh, S., Magnusdottir, D., Thorlacius, S., Thorleifsson, G., Zheng, S.L., Sun, J., Chang, B.L., Elmore, J.B., Breyer, J.P., McReynolds, K.M., Bradley, K.M., Yaspan, B.L., Wiklund, F., Stattin, P, Lindstrom, S., Adami, H.O., McDonnell, S.K., Schaid, D.J., Cunningham, J.M., Wang, L., Cerhan, J.R., Sauver, J.L. St, Isaacs, S.D., Wiley, K.E., Partin, A.W., Walsh, P.C., Polo, S., Ruiz-Echarri, M., Navarrete, S., Fuertes, F., Saez, B., Godino, J., Weijerman, P.C., Swinkels, D.W., Aben, K.K.H., Witjes, J.A., Suarez, B.K., Helfand, B.T., Frigge, M.L., Kristjansson, K., Ober, C., Jonsson, E., Einarsson, G.V., Xu, J., Gronberg, H., Smith, J.R., Thibodeau, S.N., Isaacs, W.B., Catalona, W.J., Mayordomo, J.I., Kiemeney, L.A.L.M., Barkardottir, R.B., Gulcher, J.R., Thorsteinsdottir, U., Kong, A., and Stefansson, K.

Abstract

Contains fulltext : 70723.pdf (publisher's version ) (Closed access), We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease.

Published
2008

13. Two newly identified genetic determinants of pigmentation in Europeans.

Author

Sulem, P., Gudbjartsson, D.F., Stacey, S.N., Helgason, A., Rafnar, T., Jakobsdottir, M., Steinberg, S., Gudjonsson, S.A., Palsson, A., Thorleifsson, G., Palsson, S., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Aben, K.K.H., Vermeulen, H.H.M., Goldstein, A.M., Tucker, M.A., Kiemeney, L.A.L.M., Olafsson, J.H., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., Stefansson, K., Sulem, P., Gudbjartsson, D.F., Stacey, S.N., Helgason, A., Rafnar, T., Jakobsdottir, M., Steinberg, S., Gudjonsson, S.A., Palsson, A., Thorleifsson, G., Palsson, S., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Aben, K.K.H., Vermeulen, H.H.M., Goldstein, A.M., Tucker, M.A., Kiemeney, L.A.L.M., Olafsson, J.H., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 70561.pdf (publisher's version ) (Closed access), We present results from a genome-wide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 Dutch individuals. Two coding variants in TPCN2 are associated with hair color, and a variant at the ASIP locus shows strong association with skin sensitivity to sun, freckling and red hair, phenotypic characteristics similar to those affected by well-known mutations in MC1R.

Published
2008

14. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.

Author

Gudmundsson, J., Sulem, P., Steinthorsdottir, V., Bergthorsson, J.T., Thorleifsson, G., Manolescu, A., Rafnar, T., Gudbjartsson, D.F., Agnarsson, B.A., Baker, A., Sigurdsson, A., Benediktsdottir, K.R., Jakobsdottir, M., Blondal, T., Stacey, S.N., Helgason, A., Gunnarsdottir, S., Olafsdottir, A., Kristinsson, K.T., Birgisdottir, B., Ghosh, S., Thorlacius, S., Magnusdottir, D., Stefansdottir, G., Kristjansson, K., Bagger, Y., Wilensky, R.L., Reilly, M.P., Morris, A.D., Kimber, C.H., Adeyemo, A., Chen, Y., Zhou, J., So, W.Y., Tong, P.C., Ng, M.C., Hansen, T., Andersen, G., Borch-Johnsen, K., Jorgensen, T., Tres, A., Fuertes, F., Ruiz-Echarri, M., Asin, L., Saez, B., Boven, E. van, Klaver, S., Swinkels, D.W., Aben, K.K.H., Graif, T., Cashy, J., Suarez, B.K., Vierssen Trip, O. van, Frigge, M.L., Ober, C., Hofker, M.H., Wijmenga, C., Christiansen, C., Rader, D.J., Palmer, C.N., Rotimi, C., Chan, J.C., Pedersen, O., Sigurdsson, G., Benediktsson, R., Jonsson, E., Einarsson, G.V., Mayordomo, J.I., Catalona, W.J., Kiemeney, L.A.L.M., Barkardottir, R.B., Gulcher, J.R., Thorsteinsdottir, U., Kong, A., Stefansson, K., Gudmundsson, J., Sulem, P., Steinthorsdottir, V., Bergthorsson, J.T., Thorleifsson, G., Manolescu, A., Rafnar, T., Gudbjartsson, D.F., Agnarsson, B.A., Baker, A., Sigurdsson, A., Benediktsdottir, K.R., Jakobsdottir, M., Blondal, T., Stacey, S.N., Helgason, A., Gunnarsdottir, S., Olafsdottir, A., Kristinsson, K.T., Birgisdottir, B., Ghosh, S., Thorlacius, S., Magnusdottir, D., Stefansdottir, G., Kristjansson, K., Bagger, Y., Wilensky, R.L., Reilly, M.P., Morris, A.D., Kimber, C.H., Adeyemo, A., Chen, Y., Zhou, J., So, W.Y., Tong, P.C., Ng, M.C., Hansen, T., Andersen, G., Borch-Johnsen, K., Jorgensen, T., Tres, A., Fuertes, F., Ruiz-Echarri, M., Asin, L., Saez, B., Boven, E. van, Klaver, S., Swinkels, D.W., Aben, K.K.H., Graif, T., Cashy, J., Suarez, B.K., Vierssen Trip, O. van, Frigge, M.L., Ober, C., Hofker, M.H., Wijmenga, C., Christiansen, C., Rader, D.J., Palmer, C.N., Rotimi, C., Chan, J.C., Pedersen, O., Sigurdsson, G., Benediktsson, R., Jonsson, E., Einarsson, G.V., Mayordomo, J.I., Catalona, W.J., Kiemeney, L.A.L.M., Barkardottir, R.B., Gulcher, J.R., Thorsteinsdottir, U., Kong, A., and Stefansson, K.

Abstract

Contains fulltext : 52115.pdf (publisher's version ) (Closed access), We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

Published
2007

15. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24.

Author

Gudmundsson, J., Sulem, P., Manolescu, A., Amundadottir, L.T., Gudbjartsson, D.F., Helgason, A., Rafnar, T., Bergthorsson, J.T., Agnarsson, B.A., Baker, A., Sigurdsson, A., Benediktsdottir, K.R., Jakobsdottir, M., Xu, J., Blondal, T., Kostic, J., Sun, J., Ghosh, S., Stacey, S.N., Mouy, M., Saemundsdottir, J., Backman, V.M., Kristjansson, K., Tres, A., Partin, A.W., Albers-Akkers, M.T., Marcos, J.G.I., Walsh, P.C., Swinkels, D.W., Navarrete, S., Isaacs, S.D., Aben, K.K.H., Graif, T., Cashy, J., Ruiz-Echarri, M., Wiley, K.E., Suarez, B.K., Witjes, J.A., Frigge, M., Ober, C., Jonsson, E., Einarsson, G.V., Mayordomo, J.I., Kiemeney, L.A.L.M., Isaacs, W.B., Catalona, W.J., Barkardottir, R.B., Gulcher, J.R., Thorsteinsdottir, U., Kong, A., Stefansson, K., Gudmundsson, J., Sulem, P., Manolescu, A., Amundadottir, L.T., Gudbjartsson, D.F., Helgason, A., Rafnar, T., Bergthorsson, J.T., Agnarsson, B.A., Baker, A., Sigurdsson, A., Benediktsdottir, K.R., Jakobsdottir, M., Xu, J., Blondal, T., Kostic, J., Sun, J., Ghosh, S., Stacey, S.N., Mouy, M., Saemundsdottir, J., Backman, V.M., Kristjansson, K., Tres, A., Partin, A.W., Albers-Akkers, M.T., Marcos, J.G.I., Walsh, P.C., Swinkels, D.W., Navarrete, S., Isaacs, S.D., Aben, K.K.H., Graif, T., Cashy, J., Ruiz-Echarri, M., Wiley, K.E., Suarez, B.K., Witjes, J.A., Frigge, M., Ober, C., Jonsson, E., Einarsson, G.V., Mayordomo, J.I., Kiemeney, L.A.L.M., Isaacs, W.B., Catalona, W.J., Barkardottir, R.B., Gulcher, J.R., Thorsteinsdottir, U., Kong, A., and Stefansson, K.

Abstract

Contains fulltext : 51723.pdf (publisher's version ) (Closed access), Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

Published
2007

16. Genetic determinants of hair, eye and skin pigmentation in Europeans.

Author

Sulem, P., Gudbjartsson, D.F., Stacey, S.N., Helgason, A., Rafnar, T., Magnusson, K.P., Manolescu, A., Karason, A., Palsson, A., Thorleifsson, G., Jakobsdottir, M., Steinberg, S., Palsson, S., Jonasson, F., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Aben, K.K.H., Kiemeney, L.A.L.M., Olafsson, J.H., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., Stefansson, K., Sulem, P., Gudbjartsson, D.F., Stacey, S.N., Helgason, A., Rafnar, T., Magnusson, K.P., Manolescu, A., Karason, A., Palsson, A., Thorleifsson, G., Jakobsdottir, M., Steinberg, S., Palsson, S., Jonasson, F., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Aben, K.K.H., Kiemeney, L.A.L.M., Olafsson, J.H., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 51715.pdf (publisher's version ) (Closed access), Hair, skin and eye colors are highly heritable and visible traits in humans. We carried out a genome-wide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun and freckling among 2,986 Icelanders. We then tested the most closely associated SNPs from six regions--four not previously implicated in the normal variation of human pigmentation--and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. The SNPs from all six regions met the criteria for genome-wide significance. A variant in SLC24A4 is associated with eye and hair color, a variant near KITLG is associated with hair color, two coding variants in TYR are associated with eye color and freckles, and a variant on 6p25.3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2, and the sixth encompasses previously described variants in MC1R.

Published
2007

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