排序方式: 共有40条查询结果,搜索用时 31 毫秒
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O'Donovan MC Craddock N Norton N Williams H Peirce T Moskvina V Nikolov I Hamshere M Carroll L Georgieva L Dwyer S Holmans P Marchini JL Spencer CC Howie B Leung HT Hartmann AM Möller HJ Morris DW Shi Y Feng G Hoffmann P Propping P Vasilescu C Maier W Rietschel M Zammit S Schumacher J Quinn EM Schulze TG Williams NM Giegling I Iwata N Ikeda M Darvasi A Shifman S He L Duan J Sanders AR Levinson DF Gejman PV Cichon S Nöthen MM Gill M Corvin A Rujescu D Kirov G Owen MJ Buccola NG Mowry BJ 《Nature genetics》2008,40(9):1053-1055
We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)). 相似文献
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Yeager M Orr N Hayes RB Jacobs KB Kraft P Wacholder S Minichiello MJ Fearnhead P Yu K Chatterjee N Wang Z Welch R Staats BJ Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cancel-Tassin G Cussenot O Valeri A Andriole GL Gelmann EP Tucker M Gerhard DS Fraumeni JF Hoover R Hunter DJ Chanock SJ Thomas G 《Nature genetics》2007,39(5):645-649
Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%). 相似文献
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Thomas G Jacobs KB Yeager M Kraft P Wacholder S Orr N Yu K Chatterjee N Welch R Hutchinson A Crenshaw A Cancel-Tassin G Staats BJ Wang Z Gonzalez-Bosquet J Fang J Deng X Berndt SI Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cussenot O Valeri A Andriole GL Crawford ED Tucker M Gerhard DS Fraumeni JF Hoover R Hayes RB Hunter DJ Chanock SJ 《Nature genetics》2008,40(3):310-315
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Bradfield JP Taal HR Timpson NJ Scherag A Lecoeur C Warrington NM Hypponen E Holst C Valcarcel B Thiering E Salem RM Schumacher FR Cousminer DL Sleiman PM Zhao J Berkowitz RI Vimaleswaran KS Jarick I Pennell CE Evans DM St Pourcain B Berry DJ Mook-Kanamori DO Hofman A Rivadeneira F Uitterlinden AG van Duijn CM van der Valk RJ de Jongste JC Postma DS Boomsma DI Gauderman WJ Hassanein MT Lindgren CM Mägi R Boreham CA Neville CE Moreno LA Elliott P Pouta A Hartikainen AL Li M Raitakari O 《Nature genetics》2012,44(5):526-531
Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1). 相似文献
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Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin 总被引:3,自引:0,他引:3
Small-conductance Ca2+-activated K+ channels (SK channels) are independent of voltage and gated solely by intracellular Ca2+. These membrane channels are heteromeric complexes that comprise pore-forming alpha-subunits and the Ca2+-binding protein calmodulin (CaM). CaM binds to the SK channel through the CaM-binding domain (CaMBD), which is located in an intracellular region of the alpha-subunit immediately carboxy-terminal to the pore. Channel opening is triggered when Ca2+ binds the EF hands in the N-lobe of CaM. Here we report the 1.60 A crystal structure of the SK channel CaMBD/Ca2+/CaM complex. The CaMBD forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three alpha-helices, two from one CaMBD subunit and one from the other. As only the CaM N-lobe has bound Ca2+, the structure provides a view of both calcium-dependent and -independent CaM/protein interactions. Together with biochemical data, the structure suggests a possible gating mechanism for the SK channel. 相似文献
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F. Anders F. Vester K. Klinke H. Schumacher 《Cellular and molecular life sciences : CMLS》1961,17(12):549-551
Summary The F1- and FnR-hybrids ofPlatypoecilus maculatus andXiphophorus helleri (Poeciliidae), producing melanomase spontaneously, contain essentially more free amino acids than the initial species. Further experiments show that the abnormally high content of free amino acids is connected with the spontaneous formation of tumors.
Den Herren Prof. Dr.G. de Lattin (Zoologisches Institut Saarbrücken) und Prof. Dr.B. Eistert (Institut für organische Chemie Saarbrücken) sind wir für die stete Förderung dieser Arbeit zu grösstem Dank verpflichtet. Den Herren Prof. Dr.C. Kosswig (Hamburg), Prof. Dr.M. Gordon (New York) und Dr.H. Breider (Würzburg) sind wir für viele Anregungen und die freundliche Überlassung von Zuchtstämmen sehr dankbar. — Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.
F. Anders, F. Vester, K. Klinke undH. Schumacher, Biol. Zbl., im Druck. 相似文献
Den Herren Prof. Dr.G. de Lattin (Zoologisches Institut Saarbrücken) und Prof. Dr.B. Eistert (Institut für organische Chemie Saarbrücken) sind wir für die stete Förderung dieser Arbeit zu grösstem Dank verpflichtet. Den Herren Prof. Dr.C. Kosswig (Hamburg), Prof. Dr.M. Gordon (New York) und Dr.H. Breider (Würzburg) sind wir für viele Anregungen und die freundliche Überlassung von Zuchtstämmen sehr dankbar. — Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.
F. Anders, F. Vester, K. Klinke undH. Schumacher, Biol. Zbl., im Druck. 相似文献
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