共查询到20条相似文献,搜索用时 62 毫秒
1.
Steinthorsdottir V Thorleifsson G Reynisdottir I Benediktsson R Jonsdottir T Walters GB Styrkarsdottir U Gretarsdottir S Emilsson V Ghosh S Baker A Snorradottir S Bjarnason H Ng MC Hansen T Bagger Y Wilensky RL Reilly MP Adeyemo A Chen Y Zhou J Gudnason V Chen G Huang H Lashley K Doumatey A So WY Ma RC Andersen G Borch-Johnsen K Jorgensen T van Vliet-Ostaptchouk JV Hofker MH Wijmenga C Christiansen C Rader DJ Rotimi C Gurney M Chan JC Pedersen O Sigurdsson G Gulcher JR Thorsteinsdottir U Kong A 《Nature genetics》2007,39(6):770-775
2.
Macgregor S Montgomery GW Liu JZ Zhao ZZ Henders AK Stark M Schmid H Holland EA Duffy DL Zhang M Painter JN Nyholt DR Maskiell JA Jetann J Ferguson M Cust AE Jenkins MA Whiteman DC Olsson H Puig S Bianchi-Scarrà G Hansson J Demenais F Landi MT Dębniak T Mackie R Azizi E Bressac-de Paillerets B Goldstein AM Kanetsky PA Gruis NA Elder DE Newton-Bishop JA Bishop DT Iles MM Helsing P Amos CI Wei Q Wang LE Lee JE Qureshi AA Kefford RF Giles GG Armstrong BK Aitken JF Han J Hopper JL Trent JM Brown KM 《Nature genetics》2011,43(11):1114-1118
We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density. 相似文献
3.
Shi Y Li Z Xu Q Wang T Li T Shen J Zhang F Chen J Zhou G Ji W Li B Xu Y Liu D Wang P Yang P Liu B Sun W Wan C Qin S He G Steinberg S Cichon S Werge T Sigurdsson E Tosato S Palotie A Nöthen MM Rietschel M Ophoff RA Collier DA Rujescu D Clair DS Stefansson H Stefansson K Ji J Wang Q Li W Zheng L Zhang H Feng G He L 《Nature genetics》2011,43(12):1224-1227
Schizophrenia is a severe mental disorder affecting ~1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10(-10)) and 1q24.2 (rs10489202, P = 9.50 × 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia. 相似文献
4.
Khor CC Chau TN Pang J Davila S Long HT Ong RT Dunstan SJ Wills B Farrar J Van Tram T Gan TT Binh NT Tri le T Lien le B Tuan NM Tham NT Lanh MN Nguyet NM Hieu NT Van N Vinh Chau N Thuy TT Tan DE Sakuntabhai A Teo YY Hibberd ML Simmons CP 《Nature genetics》2011,43(11):1139-1141
Hypovolemic shock (dengue shock syndrome (DSS)) is the most common life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P(meta) = 4.41 × 10(-11), per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P(meta) = 3.08 × 10(-10), per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue. 相似文献
5.
Mells GF Floyd JA Morley KI Cordell HJ Franklin CS Shin SY Heneghan MA Neuberger JM Donaldson PT Day DB Ducker SJ Muriithi AW Wheater EF Hammond CJ Dawwas MF;UK PBC Consortium;Wellcome Trust Case Control Consortium Jones DE Peltonen L Alexander GJ Sandford RN Anderson CA 《Nature genetics》2011,43(4):329-332
In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10??) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC. 相似文献
6.
Stuart PE Nair RP Ellinghaus E Ding J Tejasvi T Gudjonsson JE Li Y Weidinger S Eberlein B Gieger C Wichmann HE Kunz M Ike R Krueger GG Bowcock AM Mrowietz U Lim HW Voorhees JJ Abecasis GR Weichenthal M Franke A Rahman P Gladman DD Elder JT 《Nature genetics》2010,42(11):1000-1004
We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10?11), one at FBXL19 (rs10782001, combined P = 9 × 10?1?) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10??). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 4 × 10??; and rs12586317, combined P = 6 × 1??) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 2 × 10??; and rs12586317, combined P = 1 × 10??). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10??). 相似文献
7.
Burdon KP Macgregor S Hewitt AW Sharma S Chidlow G Mills RA Danoy P Casson R Viswanathan AC Liu JZ Landers J Henders AK Wood J Souzeau E Crawford A Leo P Wang JJ Rochtchina E Nyholt DR Martin NG Montgomery GW Mitchell P Brown MA Mackey DA Craig JE 《Nature genetics》2011,43(6):574-578
We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. 相似文献
8.
Hüffmeier U Uebe S Ekici AB Bowes J Giardina E Korendowych E Juneblad K Apel M McManus R Ho P Bruce IN Ryan AW Behrens F Lascorz J Böhm B Traupe H Lohmann J Gieger C Wichmann HE Herold C Steffens M Klareskog L Wienker TF Fitzgerald O Alenius GM McHugh NJ Novelli G Burkhardt H Barton A Reis A 《Nature genetics》2010,42(11):996-999
Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV. 相似文献
9.
Kooner JS Saleheen D Sim X Sehmi J Zhang W Frossard P Been LF Chia KS Dimas AS Hassanali N Jafar T Jowett JB Li X Radha V Rees SD Takeuchi F Young R Aung T Basit A Chidambaram M Das D Grundberg E Hedman AK Hydrie ZI Islam M Khor CC Kowlessur S Kristensen MM Liju S Lim WY Matthews DR Liu J Morris AP Nica AC Pinidiyapathirage JM Prokopenko I Rasheed A Samuel M Shah N Shera AS Small KS Suo C Wickremasinghe AR Wong TY Yang M Zhang F;DIAGRAM;MuTHER Abecasis GR Barnett AH Caulfield M Deloukas P 《Nature genetics》2011,43(10):984-989
We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D. 相似文献
10.
Haiman CA Chen GK Vachon CM Canzian F Dunning A Millikan RC Wang X Ademuyiwa F Ahmed S Ambrosone CB Baglietto L Balleine R Bandera EV Beckmann MW Berg CD Bernstein L Blomqvist C Blot WJ Brauch H Buring JE Carey LA Carpenter JE Chang-Claude J Chanock SJ Chasman DI Clarke CL Cox A Cross SS Deming SL Diasio RB Dimopoulos AM Driver WR Dünnebier T Durcan L Eccles D Edlund CK Ekici AB Fasching PA Feigelson HS Flesch-Janys D Fostira F Försti A Fountzilas G 《Nature genetics》2011,43(12):1210-1214
Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. 相似文献
11.
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
12.
Lemaire SA McDonald ML Guo DC Russell L Miller CC Johnson RJ Bekheirnia MR Franco LM Nguyen M Pyeritz RE Bavaria JE Devereux R Maslen C Holmes KW Eagle K Body SC Seidman C Seidman JG Isselbacher EM Bray M Coselli JS Estrera AL Safi HJ Belmont JW Leal SM Milewicz DM 《Nature genetics》2011,43(10):996-1000
Although thoracic aortic aneurysms and dissections (TAAD) can be inherited as a single-gene disorder, the genetic predisposition in the majority of affected people is poorly understood. In a multistage genome-wide association study (GWAS), we compared 765 individuals who had sporadic TAAD (STAAD) with 874 controls and identified common SNPs at a 15q21.1 locus that were associated with STAAD, with odds ratios of 1.6-1.8 that achieved genome-wide significance. We followed up 107 SNPs associated with STAAD with P < 1 × 10(-5) in the region, in two separate STAAD cohorts. The associated SNPs fall into a large region of linkage disequilibrium encompassing FBN1, which encodes fibrillin-1. FBN1 mutations cause Marfan syndrome, whose major cardiovascular complication is TAAD. This study shows that common genetic variants at 15q21.1 that probably act via FBN1 are associated with STAAD, suggesting a common pathogenesis of aortic disease in Marfan syndrome and STAAD. 相似文献
13.
KU Ludwig E Mangold S Herms S Nowak H Reutter A Paul J Becker R Herberz T Alchawa E Nasser AC Böhmer M Mattheisen MA Alblas S Barth N Kluck C Lauster B Braumann RH Reich A Hemprich S Pötzsch B Blaumeiser N Daratsianos T Kreusch JC Murray ML Marazita I Ruczinski AF Scott TH Beaty FJ Kramer TF Wienker RP Steegers-Theunissen M Rubini PA Mossey P Hoffmann C Lange S Cichon P Propping M Knapp MM Nöthen 《Nature genetics》2012,44(9):968-971
We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; P(NSCLP) = 6.51 × 10(-11); homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84-3.16). 相似文献
14.
Kato N Takeuchi F Tabara Y Kelly TN Go MJ Sim X Tay WT Chen CH Zhang Y Yamamoto K Katsuya T Yokota M Kim YJ Ong RT Nabika T Gu D Chang LC Kokubo Y Huang W Ohnaka K Yamori Y Nakashima E Jaquish CE Lee JY Seielstad M Isono M Hixson JE Chen YT Miki T Zhou X Sugiyama T Jeon JP Liu JJ Takayanagi R Kim SS Aung T Sung YJ Zhang X Wong TY Han BG Kobayashi S Ogihara T Zhu D Iwai N Wu JY Teo YY Tai ES Cho YS He J 《Nature genetics》2011,43(6):531-538
We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry from the AGEN-BP consortium followed up with de novo genotyping (n = 10,518) and further replication (n = 20,247) in east Asian samples. We identified genome-wide significant (P < 5 × 10(-8)) associations with SBP or DBP, which included variants at four new loci (ST7L-CAPZA1, FIGN-GRB14, ENPEP and NPR3) and a newly discovered variant near TBX3. Among the five newly discovered variants, we obtained significant replication in the independent samples for all of these loci except NPR3. We also confirmed seven loci previously identified in populations of European descent. Moreover, at 12q24.13 near ALDH2, we observed strong association signals (P = 7.9 × 10(-31) and P = 1.3 × 10(-35) for SBP and DBP, respectively) with ethnic specificity. These findings provide new insights into blood pressure regulation and potential targets for intervention. 相似文献
15.
Okada Y Kubo M Ohmiya H Takahashi A Kumasaka N Hosono N Maeda S Wen W Dorajoo R Go MJ Zheng W Kato N Wu JY Lu Q;GIANT consortium Tsunoda T Yamamoto K Nakamura Y Kamatani N Tanaka T 《Nature genetics》2012,44(3):302-306
Obesity is a disorder with a complex genetic etiology, and its epidemic is a worldwide problem. Although multiple genetic loci associated with body mass index, the most common measure of obesity, have been identified in European populations, few studies have focused on Asian populations. Here we report a genome-wide association study and replication studies with 62,245 east Asian subjects, which identified two new body mass index-associated loci in the CDKAL1 locus at 6p22 (rs2206734, P = 1.4 × 10(-11)) and the KLF9 locus at 9q21 (rs11142387, P = 1.3 × 10(-9)), as well as several previously reported loci (the SEC16B, BDNF, FTO, MC4R and GIPR loci, P < 5.0 × 10(-8)). We subsequently performed gene-gene interaction analyses and identified an interaction (P = 2.0 × 10(-8)) between a SNP in the KLF9 locus (rs11142387) and one in the MSTN (also known as GDF8) locus at 2q32 (rs13034723). These findings should provide useful insights into the etiology of obesity. 相似文献
16.
Wen W Cho YS Zheng W Dorajoo R Kato N Qi L Chen CH Delahanty RJ Okada Y Tabara Y Gu D Zhu D Haiman CA Mo Z Gao YT Saw SM Go MJ Takeuchi F Chang LC Kokubo Y Liang J Hao M Le Marchand L Zhang Y Hu Y Wong TY Long J Han BG Kubo M Yamamoto K Su MH Miki T Henderson BE Song H Tan A He J Ng DP Cai Q Tsunoda T Tsai FJ Iwai N Chen GK Shi J Xu J Sim X Xiang YB Maeda S Ong RT Li C Nakamura Y Aung T Kamatani N Liu JJ Lu W Yokota M Seielstad M 《Nature genetics》2012,44(3):307-311
Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 × 10(-8)), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 × 10(-7). Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations. 相似文献
17.
Haiman CA Chen GK Blot WJ Strom SS Berndt SI Kittles RA Rybicki BA Isaacs WB Ingles SA Stanford JL Diver WR Witte JS Hsing AW Nemesure B Rebbeck TR Cooney KA Xu J Kibel AS Hu JJ John EM Gueye SM Watya S Signorello LB Hayes RB Wang Z Yeboah E Tettey Y Cai Q Kolb S Ostrander EA Zeigler-Johnson C Yamamura Y Neslund-Dudas C Haslag-Minoff J Wu W Thomas V Allen GO Murphy A Chang BL Zheng SL Leske MC Wu SY Ray AM Hennis AJ Thun MJ Carpten J Casey G Carter EN Duarte ER Xia LY Sheng X Wan P Pooler LC 《Nature genetics》2011,43(6):570-573
In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ~5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations. 相似文献
18.
Sun LD Xiao FL Li Y Zhou WM Tang HY Tang XF Zhang H Schaarschmidt H Zuo XB Foelster-Holst R He SM Shi M Liu Q Lv YM Chen XL Zhu KJ Guo YF Hu DY Li M Li M Zhang YH Zhang X Tang JP Guo BR Wang H Liu Y Zou XY Zhou FS Liu XY Chen G Ma L Zhang SM Jiang AP Zheng XD Gao XH Li P Tu CX Yin XY Han XP Ren YQ Song SP Lu ZY Zhang XL Cui Y Chang J Gao M Luo XY Wang PG Dai X Su W Li H Shen CP Liu SX Feng XB Yang CJ Lin GS Wang ZX Huang JQ Fan X Wang Y Bao YX Yang S Liu JJ Franke A Weidinger S Yao ZR Zhang XJ 《Nature genetics》2011,43(7):690-694
Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis. 相似文献
19.
Sun LD Cheng H Wang ZX Zhang AP Wang PG Xu JH Zhu QX Zhou HS Ellinghaus E Zhang FR Pu XM Yang XQ Zhang JZ Xu AE Wu RN Xu LM Peng L Helms CA Ren YQ Zhang C Zhang SM Nair RP Wang HY Lin GS Stuart PE Fan X Chen G Tejasvi T Li P Zhu J Li ZM Ge HM Weichenthal M Ye WZ Zhang C Shen SK Yang BQ Sun YY Li SS Lin Y Jiang JH Li CT Chen RX Cheng J Jiang X Zhang P Song WM Tang J Zhang HQ Sun L Cui J Zhang LJ Tang B Huang F Qin Q Pei XP Zhou AM Shao LM Liu JL Zhang FY Du WD Franke A Bowcock AM Elder JT Liu JJ 《Nature genetics》2010,42(11):1005-1009
We extended our previous genome-wide association study for psoriasis with a multistage replication study including 8,312 individuals with psoriasis (cases) and 12,919 controls from China as well as 3,293 cases and 4,188 controls from Germany and the United States and 254 nuclear families from the United States. We identified six new susceptibility loci associated with psoriasis in the Chinese study containing the candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A (combined P < 5 × 10??) and replicated one locus, 5q33.1 (TNIP1-ANXA6), previously reported (combined P = 3.8 × 10?21) in the European studies. Two of these loci showed evidence for association in the German study at ZNF816A and GJB2 with P = 3.6 × 10?3 and P = 7.9 × 10?3, respectively. ERAP1 and ZNF816A were associated with type 1 (early onset) psoriasis in the Chinese Han population (test for heterogeneity P = 6.5 × 10?3 and P = 1.5 × 10?3, respectively). Comparisons with the results of previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between the Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis. 相似文献
20.
Identification of ten loci associated with height highlights new biological pathways in human growth 总被引:1,自引:0,他引:1
Lettre G Jackson AU Gieger C Schumacher FR Berndt SI Sanna S Eyheramendy S Voight BF Butler JL Guiducci C Illig T Hackett R Heid IM Jacobs KB Lyssenko V Uda M;Diabetes Genetics Initiative;FUSION;KORA;Prostate Lung Colorectal Ovarian Cancer Screening Trial;Nurses' Health Study;SardiNIA Boehnke M Chanock SJ Groop LC Hu FB Isomaa B Kraft P Peltonen L Salomaa V Schlessinger D Hunter DJ Hayes RB Abecasis GR Wichmann HE Mohlke KL Hirschhorn JN 《Nature genetics》2008,40(5):584-591
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. 相似文献