排序方式: 共有11条查询结果,搜索用时 15 毫秒
1.
Richards JB Yuan X Geller F Waterworth D Bataille V Glass D Song K Waeber G Vollenweider P Aben KK Kiemeney LA Walters B Soranzo N Thorsteinsdottir U Kong A Rafnar T Deloukas P Sulem P Stefansson H Stefansson K Spector TD Mooser V 《Nature genetics》2008,40(11):1282-1284
We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 x 10(-15)). 相似文献
2.
Thorgeirsson TE Geller F Sulem P Rafnar T Wiste A Magnusson KP Manolescu A Thorleifsson G Stefansson H Ingason A Stacey SN Bergthorsson JT Thorlacius S Gudmundsson J Jonsson T Jakobsdottir M Saemundsdottir J Olafsdottir O Gudmundsson LJ Bjornsdottir G Kristjansson K Skuladottir H Isaksson HJ Gudbjartsson T Jones GT Mueller T Gottsäter A Flex A Aben KK de Vegt F Mulders PF Isla D Vidal MJ Asin L Saez B Murillo L Blondal T Kolbeinsson H Stefansson JG Hansdottir I Runarsdottir V Pola R Lindblad B 《Nature》2008,452(7187):638-642
Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases. 相似文献
3.
Sulem P Gudbjartsson DF Stacey SN Helgason A Rafnar T Magnusson KP Manolescu A Karason A Palsson A Thorleifsson G Jakobsdottir M Steinberg S Pálsson S Jonasson F Sigurgeirsson B Thorisdottir K Ragnarsson R Benediktsdottir KR Aben KK Kiemeney LA Olafsson JH Gulcher J Kong A Thorsteinsdottir U Stefansson K 《Nature genetics》2007,39(12):1443-1452
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. 相似文献
4.
Stacey SN Manolescu A Sulem P Rafnar T Gudmundsson J Gudjonsson SA Masson G Jakobsdottir M Thorlacius S Helgason A Aben KK Strobbe LJ Albers-Akkers MT Swinkels DW Henderson BE Kolonel LN Le Marchand L Millastre E Andres R Godino J Garcia-Prats MD Polo E Tres A Mouy M Saemundsdottir J Backman VM Gudmundsson L Kristjansson K Bergthorsson JT Kostic J Frigge ML Geller F Gudbjartsson D Sigurdsson H Jonsdottir T Hrafnkelsson J Johannsson J Sveinsson T Myrdal G Grimsson HN Jonsson T von Holst S 《Nature genetics》2007,39(7):865-869
Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone. 相似文献
5.
Many sequence variants affecting diversity of adult human height 总被引:1,自引:0,他引:1
Gudbjartsson DF Walters GB Thorleifsson G Stefansson H Halldorsson BV Zusmanovich P Sulem P Thorlacius S Gylfason A Steinberg S Helgadottir A Ingason A Steinthorsdottir V Olafsdottir EJ Olafsdottir GH Jonsson T Borch-Johnsen K Hansen T Andersen G Jorgensen T Pedersen O Aben KK Witjes JA Swinkels DW den Heijer M Franke B Verbeek AL Becker DM Yanek LR Becker LC Tryggvadottir L Rafnar T Gulcher J Kiemeney LA Kong A Thorsteinsdottir U Stefansson K 《Nature genetics》2008,40(5):609-615
Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene. 相似文献
6.
Sulem P Gudbjartsson DF Stacey SN Helgason A Rafnar T Jakobsdottir M Steinberg S Gudjonsson SA Palsson A Thorleifsson G Pálsson S Sigurgeirsson B Thorisdottir K Ragnarsson R Benediktsdottir KR Aben KK Vermeulen SH Goldstein AM Tucker MA Kiemeney LA Olafsson JH Gulcher J Kong A Thorsteinsdottir U Stefansson K 《Nature genetics》2008,40(7):835-837
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. 相似文献
7.
Rafnar T Gudbjartsson DF Sulem P Jonasdottir A Sigurdsson A Jonasdottir A Besenbacher S Lundin P Stacey SN Gudmundsson J Magnusson OT le Roux L Orlygsdottir G Helgadottir HT Johannsdottir H Gylfason A Tryggvadottir L Jonasson JG de Juan A Ortega E Ramon-Cajal JM García-Prats MD Mayordomo C Panadero A Rivera F Aben KK van Altena AM Massuger LF Aavikko M Kujala PM Staff S Aaltonen LA Olafsdottir K Bjornsson J Kong A Salvarsdottir A Saemundsson H Olafsson K Benediktsdottir KR Gulcher J Masson G 《Nature genetics》2011,43(11):1104-1107
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 × 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. 相似文献
8.
Gudmundsson J Sulem P Manolescu A Amundadottir LT Gudbjartsson D Helgason A Rafnar T Bergthorsson JT Agnarsson BA Baker A Sigurdsson A Benediktsdottir KR Jakobsdottir M Xu J Blondal T Kostic J Sun J Ghosh S Stacey SN Mouy M Saemundsdottir J Backman VM Kristjansson K Tres A Partin AW Albers-Akkers MT Godino-Ivan Marcos J Walsh PC Swinkels DW Navarrete S Isaacs SD Aben KK Graif T Cashy J Ruiz-Echarri M Wiley KE Suarez BK Witjes JA Frigge M Ober C Jonsson E Einarsson GV Mayordomo JI Kiemeney LA 《Nature genetics》2007,39(5):631-637
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. 相似文献
9.
Kiemeney LA Thorlacius S Sulem P Geller F Aben KK Stacey SN Gudmundsson J Jakobsdottir M Bergthorsson JT Sigurdsson A Blondal T Witjes JA Vermeulen SH Hulsbergen-van de Kaa CA Swinkels DW Ploeg M Cornel EB Vergunst H Thorgeirsson TE Gudbjartsson D Gudjonsson SA Thorleifsson G Kristinsson KT Mouy M Snorradottir S Placidi D Campagna M Arici C Koppova K Gurzau E Rudnai P Kellen E Polidoro S Guarrera S Sacerdote C Sanchez M Saez B Valdivia G Ryk C de Verdier P Lindblom A Golka K Bishop DT 《Nature genetics》2008,40(11):1307-1312
We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)). 相似文献
10.
Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer
Stacey SN Manolescu A Sulem P Thorlacius S Gudjonsson SA Jonsson GF Jakobsdottir M Bergthorsson JT Gudmundsson J Aben KK Strobbe LJ Swinkels DW van Engelenburg KC Henderson BE Kolonel LN Le Marchand L Millastre E Andres R Saez B Lambea J Godino J Polo E Tres A Picelli S Rantala J Margolin S Jonsson T Sigurdsson H Jonsdottir T Hrafnkelsson J Johannsson J Sveinsson T Myrdal G Grimsson HN Sveinsdottir SG Alexiusdottir K Saemundsdottir J Sigurdsson A Kostic J Gudmundsson L Kristjansson K Masson G 《Nature genetics》2008,40(6):703-706
We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 x 10(-12) for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer. 相似文献