共查询到20条相似文献,搜索用时 15 毫秒
1.
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
2.
Ghoussaini M Fletcher O Michailidou K Turnbull C Schmidt MK Dicks E Dennis J Wang Q Humphreys MK Luccarini C Baynes C Conroy D Maranian M Ahmed S Driver K Johnson N Orr N dos Santos Silva I Waisfisz Q Meijers-Heijboer H Uitterlinden AG Rivadeneira F;Netherlands Collaborative Group on Hereditary Breast Ovarian Cancer 《Nature genetics》2012,44(3):312-318
Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ~8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ~70,000 cases and ~68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth. 相似文献
3.
Freilinger T Anttila V de Vries B Malik R Kallela M Terwindt GM Pozo-Rosich P Winsvold B Nyholt DR van Oosterhout WP Artto V Todt U Hämäläinen E Fernández-Morales J Louter MA Kaunisto MA Schoenen J Raitakari O Lehtimäki T Vila-Pueyo M Göbel H Wichmann E Sintas C Uitterlinden AG Hofman A Rivadeneira F Heinze A Tronvik E van Duijn CM Kaprio J Cormand B Wessman M Frants RR Meitinger T Müller-Myhsok B Zwart JA Färkkilä M Macaya A Ferrari MD Kubisch C Palotie A Dichgans M 《Nature genetics》2012,44(7):777-782
Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10(-4); combined P = 7.06 × 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 × 10(-4); combined P = 1.17 × 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10(-8) and P = 0.02; combined P = 3.86 × 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. 相似文献
4.
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
5.
Barrett JH Iles MM Harland M Taylor JC Aitken JF Andresen PA Akslen LA Armstrong BK Avril MF Azizi E Bakker B Bergman W Bianchi-Scarrà G Bressac-de Paillerets B Calista D Cannon-Albright LA Corda E Cust AE Dębniak T Duffy D Dunning AM Easton DF Friedman E Galan P Ghiorzo P Giles GG Hansson J Hocevar M Höiom V Hopper JL Ingvar C Janssen B Jenkins MA Jönsson G Kefford RF Landi G Landi MT Lang J Lubiński J Mackie R Malvehy J Martin NG Molven A Montgomery GW van Nieuwpoort FA Novakovic S Olsson H 《Nature genetics》2011,43(11):1108-1113
We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 × 10(-9)), an SNP in MX2 (rs45430, P = 2.9 × 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series. 相似文献
6.
Gharavi AG Kiryluk K Choi M Li Y Hou P Xie J Sanna-Cherchi S Men CJ Julian BA Wyatt RJ Novak J He JC Wang H Lv J Zhu L Wang W Wang Z Yasuno K Gunel M Mane S Umlauf S Tikhonova I Beerman I Savoldi S Magistroni R Ghiggeri GM Bodria M Lugani F Ravani P Ponticelli C Allegri L Boscutti G Frasca G Amore A Peruzzi L Coppo R Izzi C Viola BF Prati E Salvadori M Mignani R Gesualdo L Bertinetto F Mesiano P Amoroso A Scolari F Chen N Zhang H Lifton RP 《Nature genetics》2011,43(4):321-327
We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 × 10?2? and 4.84 × 10?? and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures. 相似文献
7.
Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population 总被引:1,自引:0,他引:1
Arakawa S Takahashi A Ashikawa K Hosono N Aoi T Yasuda M Oshima Y Yoshida S Enaida H Tsuchihashi T Mori K Honda S Negi A Arakawa A Kadonosono K Kiyohara Y Kamatani N Nakamura Y Ishibashi T Kubo M 《Nature genetics》2011,43(10):1001-1004
8.
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
9.
Albagha OM Wani SE Visconti MR Alonso N Goodman K Brandi ML Cundy T Chung PY Dargie R Devogelaer JP Falchetti A Fraser WD Gennari L Gianfrancesco F Hooper MJ Van Hul W Isaia G Nicholson GC Nuti R Papapoulos S Montes Jdel P Ratajczak T Rea SL Rendina D Gonzalez-Sarmiento R Di Stefano M Ward LC Walsh JP Ralston SH;Genetic Determinants of Paget's Disease 《Nature genetics》2011,43(7):685-689
Paget's disease of bone (PDB) is a common disorder characterized by focal abnormalities of bone remodeling. We previously identified variants at the CSF1, OPTN and TNFRSF11A loci as risk factors for PDB by genome-wide association study. Here we extended this study, identified three new loci and confirmed their association with PDB in 2,215 affected individuals (cases) and 4,370 controls from seven independent populations. The new associations were with rs5742915 within PML on 15q24 (odds ratio (OR) = 1.34, P = 1.6 × 10(-14)), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10(-11)) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10(-10)). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10(-17)) with PDB. These seven loci explained ~13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB. 相似文献
10.
Weedon MN Lango H Lindgren CM Wallace C Evans DM Mangino M Freathy RM Perry JR Stevens S Hall AS Samani NJ Shields B Prokopenko I Farrall M Dominiczak A;Diabetes Genetics Initiative;Wellcome Trust Case Control Consortium Johnson T Bergmann S Beckmann JS Vollenweider P Waterworth DM Mooser V Palmer CN Morris AD Ouwehand WH;Cambridge GEM Consortium Zhao JH Li S Loos RJ Barroso I Deloukas P Sandhu MS Wheeler E Soranzo N Inouye M Wareham NJ Caulfield M Munroe PB Hattersley AT McCarthy MI Frayling TM 《Nature genetics》2008,40(5):575-583
Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait. 相似文献
11.
Schizophrenia Psychiatric Genome-Wide Association Study 《Nature genetics》2011,43(10):969-976
12.
Hirota T Takahashi A Kubo M Tsunoda T Tomita K Doi S Fujita K Miyatake A Enomoto T Miyagawa T Adachi M Tanaka H Niimi A Matsumoto H Ito I Masuko H Sakamoto T Hizawa N Taniguchi M Lima JJ Irvin CG Peters SP Himes BE Litonjua AA Tantisira KG Weiss ST Kamatani N Nakamura Y Tamari M 《Nature genetics》2011,43(9):893-896
Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility. 相似文献
13.
Lu X Wang L Chen S He L Yang X Shi Y Cheng J Zhang L Gu CC Huang J Wu T Ma Y Li J Cao J Chen J Ge D Fan Z Li Y Zhao L Li H Zhou X Chen L Liu D Chen J Duan X Hao Y Wang L Lu F Liu Z Yao C Shen C Pu X Yu L Fang X Xu L Mu J Wu X Zheng R Wu N Zhao Q Li Y Liu X Wang M Yu D Hu D Ji X Guo D Sun D Wang Q Yang Y Liu F Mao Q Liang X Ji J Chen P Mo X Li D Chai G Tang Y Li X Du Z Liu X Dou C Yang Z Meng Q Wang D Wang R Yang J Schunkert H Samani NJ Kathiresan S Reilly MP 《Nature genetics》2012,44(8):890-894
We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 × 10(-8)). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population. 相似文献
14.
Wu C Miao X Huang L Che X Jiang G Yu D Yang X Cao G Hu Z Zhou Y Zuo C Wang C Zhang X Zhou Y Yu X Dai W Li Z Shen H Liu L Chen Y Zhang S Wang X Zhai K Chang J Liu Y Sun M Cao W Gao J Ma Y Zheng X Cheung ST Jia Y Xu J Tan W Zhao P Wu T Wang C Lin D 《Nature genetics》2012,44(1):62-66
Pancreatic cancer has the lowest survival rate among human cancers, and there are no effective markers for its screening and early diagnosis. To identify genetic susceptibility markers for this cancer, we carried out a genome-wide association study on 981 individuals with pancreatic cancer (cases) and 1,991 cancer-free controls of Chinese descent using 666,141 autosomal SNPs. Promising associations were replicated in an additional 2,603 pancreatic cancer cases and 2,877 controls recruited from 25 hospitals in 16 provinces or cities in China. We identified five new susceptibility loci at chromosomes 21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11 (P = 2.24 × 10(-13) to P = 4.18 × 10(-10)) in addition to 13q22.1 previously reported in populations of European ancestry. These results advance our understanding of the development of pancreatic cancer and highlight potential targets for the prevention or treatment of this cancer. 相似文献
15.
Wu C Hu Z He Z Jia W Wang F Zhou Y Liu Z Zhan Q Liu Y Yu D Zhai K Chang J Qiao Y Jin G Liu Z Shen Y Guo C Fu J Miao X Tan W Shen H Ke Y Zeng Y Wu T Lin D 《Nature genetics》2011,43(7):679-684
Esophageal squamous-cell carcinoma (ESCC) is one of the most prevalent cancers worldwide and occurs at a relatively high frequency in China. To identify genetic susceptibility loci for ESCC, we conducted a genome-wide association study on 2,031 individuals with ESCC (cases) and 2,044 controls of Chinese descent using 666,141 autosomal SNPs. We evaluated promising associations in an additional 6,276 cases and 6,165 controls of Chinese descent from different areas of China. We identified seven susceptibility loci on chromosomes 5q11, 6p21, 10q23, 12q24 and 21q22 (ranging from P = 7.48 × 10(-12) to P = 2.44 × 10(-31)); among these loci, 5q11, 6p21 and 21q22 were newly identified. Three variants in high linkage disequilibrium on 12q24 confer their risks to ESCC in a gene-lifestyle interaction manner, with more pronounced risk enhancement seen in tobacco and alcohol users. Furthermore, the identified variants had a cumulative association with ESCC risk (P(trend) = 7.92 × 10(-56)). These findings highlight the involvement of multiple genetic loci and gene-environment interaction in the development of esophageal cancer. 相似文献
16.
Purdue MP Johansson M Zelenika D Toro JR Scelo G Moore LE Prokhortchouk E Wu X Kiemeney LA Gaborieau V Jacobs KB Chow WH Zaridze D Matveev V Lubinski J Trubicka J Szeszenia-Dabrowska N Lissowska J Rudnai P Fabianova E Bucur A Bencko V Foretova L Janout V Boffetta P Colt JS Davis FG Schwartz KL Banks RE Selby PJ Harnden P Berg CD Hsing AW Grubb RL Boeing H Vineis P Clavel-Chapelon F Palli D Tumino R Krogh V Panico S Duell EJ Quirós JR Sanchez MJ Navarro C Ardanaz E Dorronsoro M Khaw KT Allen NE 《Nature genetics》2011,43(1):60-65
17.
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
18.
Rioux JD Xavier RJ Taylor KD Silverberg MS Goyette P Huett A Green T Kuballa P Barmada MM Datta LW Shugart YY Griffiths AM Targan SR Ippoliti AF Bernard EJ Mei L Nicolae DL Regueiro M Schumm LP Steinhart AH Rotter JI Duerr RH Cho JH Daly MJ Brant SR 《Nature genetics》2007,39(5):596-604
We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease. 相似文献
19.
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
20.
Schunkert H König IR Kathiresan S Reilly MP Assimes TL Holm H Preuss M Stewart AF Barbalic M Gieger C Absher D Aherrahrou Z Allayee H Altshuler D Anand SS Andersen K Anderson JL Ardissino D Ball SG Balmforth AJ Barnes TA Becker DM Becker LC Berger K Bis JC Boekholdt SM Boerwinkle E Braund PS Brown MJ Burnett MS Buysschaert I;Cardiogenics Carlquist JF Chen L Cichon S Codd V Davies RW Dedoussis G Dehghan A Demissie S Devaney JM Diemert P Do R Doering A Eifert S Mokhtari NE Ellis SG Elosua R 《Nature genetics》2011,43(4):333-338
We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10?? and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. 相似文献