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A genome-wide association search for type 2 diabetes genes in African Americans.

Nicholette D Palmer | Caitrin W McDonough | Pamela J Hicks | Bong H Roh | Maria R Wing | S Sandy An | Jessica M Hester | Jessica N Cooke | Meredith A Bostrom | Megan E Rudock | Matthew E Talbert | Joshua P Lewis | DIAGRAM Consortium | MAGIC Investigators | Assiamira Ferrara | Lingyi Lu | Julie T Ziegler | Michele M Sale | Jasmin Divers | Daniel Shriner | Adebowale Adeyemo | Charles N Rotimi | Maggie C Y Ng | Carl D Langefeld | Barry I Freedman | Donald W Bowden | Benjamin F Voight | Laura J Scott | Valgerdur Steinthorsdottir | Andrew P Morris | Christian Dina | Ryan P Welch | Eleftheria Zeggini | Cornelia Huth | Yurii S Aulchenko | Gudmar Thorleifsson | Laura J McCulloch | Teresa Ferreira | Harald Grallert | Najaf Amin | Guanming Wu | Cristen J Willer | Soumya Raychaudhuri | Steve A McCarroll | Claudia Langenberg | Oliver M Hofmann | Josée Dupuis | Lu Qi | Ayellet V Segrè | Mandy van Hoek | Pau Navarro | Kristin Ardlie | Beverley Balkau | Rafn Benediktsson | Amanda J Bennett | Roza Blagieva | Eric Boerwinkle | Lori L Bonnycastle | Kristina Bengtsson Boström | Bert Bravenboer | Suzannah Bumpstead | Noël P Burtt | Guillaume Charpentier | Peter S Chines | Marilyn Cornelis | David J Couper | Gabe Crawford | Alex S F Doney | Katherine S Elliott | Amanda L Elliott | Michael R Erdos | Caroline S Fox | Christopher S Franklin | Martha Ganser | Christian Gieger | Niels Grarup | Todd Green | Simon Griffin | Christopher J Groves | Candace Guiducci | Samy Hadjadj | Neelam Hassanali | Christian Herder | Bo Isomaa | Anne U Jackson | Paul R V Johnson | Torben Jørgensen | Wen H L Kao | Norman Klopp | Augustine Kong | Peter Kraft | Johanna Kuusisto | Torsten Lauritzen | Man Li | Aloysius Lieverse | Cecilia M Lindgren | Valeriya Lyssenko | Michel Marre | Thomas Meitinger | Kristian Midthjell | Mario A Morken | Narisu Narisu | Peter Nilsson | Katharine R Owen | Felicity Payne | John R B Perry | Ann-Kristin Petersen | Carl Platou | Christine Proença | Inga Prokopenko | Wolfgang Rathmann | N William Rayner | Neil R Robertson | Ghislain Rocheleau | Michael Roden | Michael J Sampson | Richa Saxena | Beverley M Shields | Peter Shrader | Gunnar Sigurdsson | Thomas Sparsø | Klaus Strassburger | Heather M Stringham | Qi Sun | Amy J Swift | Barbara Thorand | Jean Tichet | Tiinamaija Tuomi | Rob M van Dam | Timon W van Haeften | Thijs van Herpt | Jana V van Vliet-Ostaptchouk | G Bragi Walters | Michael N Weedon | Cisca Wijmenga | Jacqueline Witteman | Richard N Bergman | Stephane Cauchi | Francis S Collins | Anna L Gloyn | Ulf Gyllensten | Torben Hansen | Winston A Hide | Graham A Hitman | Albert Hofman | David J Hunter | Kristian Hveem | Markku Laakso | Karen L Mohlke | Andrew D Morris | Colin N A Palmer | Peter P Pramstaller | Igor Rudan | Eric Sijbrands | Lincoln D Stein | Jaakko Tuomilehto | Andre Uitterlinden | Mark Walker | Nicholas J Wareham | Richard M Watanabe | Goncalo R Abecasis | Bernhard O Boehm | Harry Campbell | Mark J Daly | Andrew T Hattersley | Frank B Hu | James B Meigs | James S Pankow | Oluf Pedersen | H-Erich Wichmann | Inês Barroso | Jose C Florez | Timothy M Frayling | Leif Groop | Rob Sladek | Unnur Thorsteinsdottir | James F Wilson | Thomas Illig | Philippe Froguel | Cornelia M van Duijn | Kari Stefansson | David Altshuler | Michael Boehnke | Mark I McCarthy | Nicole Soranzo | Eleanor Wheeler | Nicole L Glazer | Nabila Bouatia-Naji | Reedik Mägi | Joshua Randall | Toby Johnson | Paul Elliott | Denis Rybin | Peter Henneman | Abbas Dehghan | Jouke Jan Hottenga | Kijoung Song | Anuj Goel | Josephine M Egan | Taina Lajunen | Alex Doney | Stavroula Kanoni | Christine Cavalcanti-Proença | Meena Kumari | Nicholas J Timpson | Carina Zabena | Erik Ingelsson | Ping An | Jeffrey O'Connell | Jian'an Luan | Amanda Elliott | Steven A McCarroll | Rosa Maria Roccasecca | François Pattou | Praveen Sethupathy | Yavuz Ariyurek | Philip Barter | John P Beilby | Yoav Ben-Shlomo | Sven Bergmann | Murielle Bochud | Amélie Bonnefond | Knut Borch-Johnsen | Yvonne Böttcher | Eric Brunner | Suzannah J Bumpstead | Yii-Der Ida Chen | Peter Chines | Robert Clarke | Lachlan J M Coin | Matthew N Cooper | Laura Crisponi | Ian N M Day | Eco J C de Geus | Jerome Delplanque | Annette C Fedson | Antje Fischer-Rosinsky | Nita G Forouhi | Rune Frants | Maria Grazia Franzosi | Pilar Galan | Mark O Goodarzi | Jürgen Graessler | Scott Grundy | Rhian Gwilliam | Göran Hallmans | Naomi Hammond | Xijing Han | Anna-Liisa Hartikainen | Caroline Hayward | Simon C Heath | Serge Hercberg | Andrew A Hicks | David R Hillman | Aroon D Hingorani | Jennie Hui | Joe Hung | Antti Jula | Marika Kaakinen | Jaakko Kaprio | Y Antero Kesaniemi | Mika Kivimaki | Beatrice Knight | Seppo Koskinen | Peter Kovacs | Kirsten Ohm Kyvik | G Mark Lathrop | Debbie A Lawlor | Olivier Le Bacquer | Cécile Lecoeur | Yun Li | Robert Mahley | Massimo Mangino | Alisa K Manning | María Teresa Martínez-Larrad | Jarred B McAteer | Ruth McPherson | Christa Meisinger | David Melzer | David Meyre | Braxton D Mitchell | Sutapa Mukherjee | Silvia Naitza | Matthew J Neville | Ben A Oostra | Marco Orrù | Ruth Pakyz | Giuseppe Paolisso | Cristian Pattaro | Daniel Pearson | John F Peden | Nancy L Pedersen | Markus Perola | Andreas F H Pfeiffer | Irene Pichler | Ozren Polasek | Danielle Posthuma | Simon C Potter | Anneli Pouta | Michael A Province | Bruce M Psaty | Nigel W Rayner | Kenneth Rice | Samuli Ripatti | Fernando Rivadeneira | Olov Rolandsson | Annelli Sandbaek | Manjinder Sandhu | Serena Sanna | Avan Aihie Sayer | Paul Scheet | Udo Seedorf | Stephen J Sharp | Beverley Shields | Eric J G Sijbrands | Angela Silveira | Laila Simpson | Andrew Singleton | Nicholas L Smith | Ulla Sovio | Amy Swift | Holly Syddall | Ann-Christine Syvänen | Toshiko Tanaka | Anke Tönjes | André G Uitterlinden | Ko Willems van Dijk | Dhiraj Varma | Sophie Visvikis-Siest | Veronique Vitart | Nicole Vogelzangs | Gérard Waeber | Peter J Wagner | Andrew Walley | Kim L Ward | Hugh Watkins | Sarah H Wild | Gonneke Willemsen | Jaqueline C M Witteman | John W G Yarnell | Diana Zelenika | Björn Zethelius | Guangju Zhai | Jing Hua Zhao | M Carola Zillikens | Ingrid B Borecki | Ruth J F Loos | Pierre Meneton | Patrik K E Magnusson | David M Nathan | Gordon H Williams | Kaisa Silander | Veikko Salomaa | George Davey Smith | Stefan R Bornstein | Peter Schwarz | Joachim Spranger | Fredrik Karpe | Alan R Shuldiner | Cyrus Cooper | George V Dedoussis | Manuel Serrano-Ríos | Lars Lind | Lyle J Palmer | Paul W Franks | Shah Ebrahim | Michael Marmot | W H Linda Kao | Peter Paul Pramstaller | Alan F Wright | Michael Stumvoll | Anders Hamsten | Thomas A Buchanan | Timo T Valle | Jerome I Rotter | David S Siscovick | Brenda W J H Penninx | Dorret I Boomsma | Panos Deloukas | Timothy D Spector | Luigi Ferrucci | Antonio Cao | Angelo Scuteri | David Schlessinger | Manuela Uda | Aimo Ruokonen | Marjo-Riitta Jarvelin | Dawn M Waterworth | Peter Vollenweider | Leena Peltonen | Vincent Mooser | Robert Sladek
PloS one | 2012

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Pubmed ID: 22238593 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MC_U127592696
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UP_A100_1003
  • Agency: Medical Research Council, United Kingdom
    Id: G0801056
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR000124
  • Agency: Medical Research Council, United Kingdom
    Id: G0902037
  • Agency: NIDDK NIH HHS, United States
    Id: K24 DK080140
  • Agency: NCRR NIH HHS, United States
    Id: M01 RR07122
  • Agency: Medical Research Council, United Kingdom
    Id: G0001164
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/07/008/23674
  • Agency: Medical Research Council, United Kingdom
    Id: G19/35
  • Agency: Medical Research Council, United Kingdom
    Id: G8802774
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UP_A620_1015
  • Agency: Medical Research Council, United Kingdom
    Id: MC_U106179474
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL56266
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK070941
  • Agency: NIDDK NIH HHS, United States
    Id: R00 DK081350
  • Agency: Medical Research Council, United Kingdom
    Id: G0100222
  • Agency: PHS HHS, United States
    Id: HHSC268200782096C
  • Agency: Medical Research Council, United Kingdom
    Id: MC_U127561128
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK079637
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063491
  • Agency: NIDDK NIH HHS, United States
    Id: K99 DK081350
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK066358
  • Agency: NIDDK NIH HHS, United States
    Id: K08 DK002600
  • Agency: Wellcome Trust, United Kingdom
    Id: 090532
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_U127561128
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_U127592696
  • Agency: NCRR NIH HHS, United States
    Id: M01 RR007122
  • Agency: NHLBI NIH HHS, United States
    Id: K99 HL098459
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK053591
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Department of Health, United Kingdom
    Id: DHCS/07/07/008
  • Agency: Medical Research Council, United Kingdom
    Id: MC_U106179471

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This is a list of tools and resources that we have found mentioned in this publication.


PLINK (tool)

RRID:SCR_001757

Open source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.

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METAL (tool)

RRID:SCR_002013

Software application designed to facilitate meta-analysis of large datasets (such as several whole genome scans) in a convenient, rapid and memory efficient manner. (entry from Genetic Analysis Software)

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Haploview (tool)

RRID:SCR_003076

A Java based software tool designed to simplify and expedite the process of haplotype analysis by providing a common interface to several tasks relating to such analyses. Haploview currently allows users to examine block structures, generate haplotypes in these blocks, run association tests, and save the data in a number of formats. All functionalities are highly customizable. (entry from Genetic Analysis Software) * LD & haplotype block analysis * haplotype population frequency estimation * single SNP and haplotype association tests * permutation testing for association significance * implementation of Paul de Bakker's Tagger tag SNP selection algorithm. * automatic download of phased genotype data from HapMap * visualization and plotting of PLINK whole genome association results including advanced filtering options Haploview is fully compatible with data dumps from the HapMap project and the Perlegen Genotype Browser. It can analyze thousands of SNPs (tens of thousands in command line mode) in thousands of individuals. Note: Haploview is currently on a development and support freeze. The team is currently looking at a variety of options in order to provide support for the software. Haploview is an open source project hosted by SourceForge. The source can be downloaded at the SourceForge project site.

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International HapMap Project (tool)

RRID:SCR_002846

THIS RESOURCE IS NO LONGER IN SERVICE, documented August 22, 2016. A multi-country collaboration among scientists and funding agencies to develop a public resource where genetic similarities and differences in human beings are identified and catalogued. Using this information, researchers will be able to find genes that affect health, disease, and individual responses to medications and environmental factors. All of the information generated by the Project will be released into the public domain. Their goal is to compare the genetic sequences of different individuals to identify chromosomal regions where genetic variants are shared. Public and private organizations in six countries are participating in the International HapMap Project. Data generated by the Project can be downloaded with minimal constraints. HapMap project related data, software, and documentation include: bulk data on genotypes, frequencies, LD data, phasing data, allocated SNPs, recombination rates and hotspots, SNP assays, Perlegen amplicons, raw data, inferred genotypes, and mitochondrial and chrY haplogroups; Generic Genome Browser software; protocols and information on assay design, genotyping and other protocols used in the project; and documentation of samples/individuals and the XML format used in the project.

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MACH (tool)

RRID:SCR_009621

QTL analysis based on imputed dosages/posterior_probabilities.

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