Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23222517
TITLE
Seventy-five genetic loci influencing the human red blood cell.
ABSTRACT
Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
DATE PUBLISHED
2012 Dec 20
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/02/06
accepted 2012/10/15
aheadofprint 2012/12/05
entrez 2012/12/11 06:00
pubmed 2012/12/12 06:00
medline 2013/02/13 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
van der Harst P van der Harst Pim P Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. p.van.der.harst@umcg.nl
Zhang W Zhang Weihua W
Mateo Leach I Mateo Leach Irene I
Rendon A Rendon Augusto A
Verweij N Verweij Niek N
Sehmi J Sehmi Joban J
Paul DS Paul Dirk S DS
Elling U Elling Ulrich U
Allayee H Allayee Hooman H
Li X Li Xinzhong X
Radhakrishnan A Radhakrishnan Aparna A
Tan ST Tan Sian-Tsung ST
Voss K Voss Katrin K
Weichenberger CX Weichenberger Christian X CX
Albers CA Albers Cornelis A CA
Al-Hussani A Al-Hussani Abtehale A
Asselbergs FW Asselbergs Folkert W FW
Ciullo M Ciullo Marina M
Danjou F Danjou Fabrice F
Dina C Dina Christian C
Esko T Esko Tõnu T
Evans DM Evans David M DM
Franke L Franke Lude L
Gögele M Gögele Martin M
Hartiala J Hartiala Jaana J
Hersch M Hersch Micha M
Holm H Holm Hilma H
Hottenga JJ Hottenga Jouke-Jan JJ
Kanoni S Kanoni Stavroula S
Kleber ME Kleber Marcus E ME
Lagou V Lagou Vasiliki V
Langenberg C Langenberg Claudia C
Lopez LM Lopez Lorna M LM
Lyytikäinen LP Lyytikäinen Leo-Pekka LP
Melander O Melander Olle O
Murgia F Murgia Federico F
Nolte IM Nolte Ilja M IM
O'Reilly PF O'Reilly Paul F PF
Padmanabhan S Padmanabhan Sandosh S
Parsa A Parsa Afshin A
Pirastu N Pirastu Nicola N
Porcu E Porcu Eleonora E
Portas L Portas Laura L
Prokopenko I Prokopenko Inga I
Ried JS Ried Janina S JS
Shin SY Shin So-Youn SY
Tang CS Tang Clara S CS
Teumer A Teumer Alexander A
Traglia M Traglia Michela M
Ulivi S Ulivi Sheila S
Westra HJ Westra Harm-Jan HJ
Yang J Yang Jian J
Zhao JH Zhao Jing Hua JH
Anni F Anni Franco F
Abdellaoui A Abdellaoui Abdel A
Attwood A Attwood Antony A
Balkau B Balkau Beverley B
Bandinelli S Bandinelli Stefania S
Bastardot F Bastardot François F
Benyamin B Benyamin Beben B
Boehm BO Boehm Bernhard O BO
Cookson WO Cookson William O WO
Das D Das Debashish D
de Bakker PI de Bakker Paul I W PI
de Boer RA de Boer Rudolf A RA
de Geus EJ de Geus Eco J C EJ
de Moor MH de Moor Marleen H MH
Dimitriou M Dimitriou Maria M
Domingues FS Domingues Francisco S FS
Döring A Döring Angela A
Engström G Engström Gunnar G
Eyjolfsson GI Eyjolfsson Gudmundur Ingi GI
Ferrucci L Ferrucci Luigi L
Fischer K Fischer Krista K
Galanello R Galanello Renzo R
Garner SF Garner Stephen F SF
Genser B Genser Bernd B
Gibson QD Gibson Quince D QD
Girotto G Girotto Giorgia G
Gudbjartsson DF Gudbjartsson Daniel Fannar DF
Harris SE Harris Sarah E SE
Hartikainen AL Hartikainen Anna-Liisa AL
Hastie CE Hastie Claire E CE
Hedblad B Hedblad Bo B
Illig T Illig Thomas T
Jolley J Jolley Jennifer J
Kähönen M Kähönen Mika M
Kema IP Kema Ido P IP
Kemp JP Kemp John P JP
Liang L Liang Liming L
Lloyd-Jones H Lloyd-Jones Heather H
Loos RJ Loos Ruth J F RJ
Meacham S Meacham Stuart S
Medland SE Medland Sarah E SE
Meisinger C Meisinger Christa C
Memari Y Memari Yasin Y
Mihailov E Mihailov Evelin E
Miller K Miller Kathy K
Moffatt MF Moffatt Miriam F MF
Nauck M Nauck Matthias M
Novatchkova M Novatchkova Maria M
Nutile T Nutile Teresa T
Olafsson I Olafsson Isleifur I
Onundarson PT Onundarson Pall T PT
Parracciani D Parracciani Debora D
Penninx BW Penninx Brenda W BW
Perseu L Perseu Lucia L
Piga A Piga Antonio A
Pistis G Pistis Giorgio G
Pouta A Pouta Anneli A
Puc U Puc Ursula U
Raitakari O Raitakari Olli O
Ring SM Ring Susan M SM
Robino A Robino Antonietta A
Ruggiero D Ruggiero Daniela D
Ruokonen A Ruokonen Aimo A
Saint-Pierre A Saint-Pierre Aude A
Sala C Sala Cinzia C
Salumets A Salumets Andres A
Sambrook J Sambrook Jennifer J
Schepers H Schepers Hein H
Schmidt CO Schmidt Carsten Oliver CO
Silljé HH Silljé Herman H W HH
Sladek R Sladek Rob R
Smit JH Smit Johannes H JH
Starr JM Starr John M JM
Stephens J Stephens Jonathan J
Sulem P Sulem Patrick P
Tanaka T Tanaka Toshiko T
Thorsteinsdottir U Thorsteinsdottir Unnur U
Tragante V Tragante Vinicius V
van Gilst WH van Gilst Wiek H WH
van Pelt LJ van Pelt L Joost LJ
van Veldhuisen DJ van Veldhuisen Dirk J DJ
Völker U Völker Uwe U
Whitfield JB Whitfield John B JB
Willemsen G Willemsen Gonneke G
Winkelmann BR Winkelmann Bernhard R BR
Wirnsberger G Wirnsberger Gerald G
Algra A Algra Ale A
Cucca F Cucca Francesco F
d'Adamo AP d'Adamo Adamo Pio AP
Danesh J Danesh John J
Deary IJ Deary Ian J IJ
Dominiczak AF Dominiczak Anna F AF
Elliott P Elliott Paul P
Fortina P Fortina Paolo P
Froguel P Froguel Philippe P
Gasparini P Gasparini Paolo P
Greinacher A Greinacher Andreas A
Hazen SL Hazen Stanley L SL
Jarvelin MR Jarvelin Marjo-Riitta MR
Khaw KT Khaw Kay Tee KT
Lehtimäki T Lehtimäki Terho T
Maerz W Maerz Winfried W
Martin NG Martin Nicholas G NG
Metspalu A Metspalu Andres A
Mitchell BD Mitchell Braxton D BD
Montgomery GW Montgomery Grant W GW
Moore C Moore Carmel C
Navis G Navis Gerjan G
Pirastu M Pirastu Mario M
Pramstaller PP Pramstaller Peter P PP
Ramirez-Solis R Ramirez-Solis Ramiro R
Schadt E Schadt Eric E
Scott J Scott James J
Shuldiner AR Shuldiner Alan R AR
Smith GD Smith George Davey GD
Smith JG Smith J Gustav JG
Snieder H Snieder Harold H
Sorice R Sorice Rossella R
Spector TD Spector Tim D TD
Stefansson K Stefansson Kari K
Stumvoll M Stumvoll Michael M
Tang WH Tang W H Wilson WH
Toniolo D Toniolo Daniela D
Tönjes A Tönjes Anke A
Visscher PM Visscher Peter M PM
Vollenweider P Vollenweider Peter P
Wareham NJ Wareham Nicholas J NJ
Wolffenbuttel BH Wolffenbuttel Bruce H R BH
Boomsma DI Boomsma Dorret I DI
Beckmann JS Beckmann Jacques S JS
Dedoussis GV Dedoussis George V GV
Deloukas P Deloukas Panos P
Ferreira MA Ferreira Manuel A MA
Sanna S Sanna Serena S
Uda M Uda Manuela M
Hicks AA Hicks Andrew A AA
Penninger JM Penninger Josef Martin JM
Gieger C Gieger Christian C
Kooner JS Kooner Jaspal S JS
Ouwehand WH Ouwehand Willem H WH
Soranzo N Soranzo Nicole N
Chambers JC Chambers John C JC
INVESTIGATORS
JOURNAL
VOLUME: 492
ISSUE: 7429
TITLE: Nature
ISOABBREVIATION: Nature
YEAR: 2012
MONTH: Dec
DAY: 20
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-4687
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nature
COUNTRY: England
ISSNLINKING: 0028-0836
NLMUNIQUEID: 0410462
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
092731 Wellcome Trust United Kingdom
097117 Wellcome Trust United Kingdom
14136 Cancer Research UK United Kingdom
CZB/4/505 Chief Scientist Office United Kingdom
ETM/55 Chief Scientist Office United Kingdom
G0600705 Medical Research Council United Kingdom
G0700704 Medical Research Council United Kingdom
G0801056 Medical Research Council United Kingdom
G1000143 Medical Research Council United Kingdom
G1002084 Medical Research Council United Kingdom
G9815508 Medical Research Council United Kingdom
HHSN268201100005C NHLBI NIH HHS United States
HHSN268201100006C NHLBI NIH HHS United States
HHSN268201100007C NHLBI NIH HHS United States
HHSN268201100008C NHLBI NIH HHS United States
HHSN268201100009C NHLBI NIH HHS United States
HHSN268201100010C NHLBI NIH HHS United States
HHSN268201100011C NHLBI NIH HHS United States
HHSN268201100012C NHLBI NIH HHS United States
HHSN271201100005C NIDA NIH HHS United States
K12 RR023250 NCRR NIH HHS United States
MC_PC_15018 Medical Research Council United Kingdom
MC_U106179471 Medical Research Council United Kingdom
MC_U106188470 Medical Research Council United Kingdom
N01AG12109 NIA NIH HHS United States
P01 HL076491 NHLBI NIH HHS United States
P01 HL098055 NHLBI NIH HHS United States
P20 HL113452 NHLBI NIH HHS United States
P30 DK072488 NIDDK NIH HHS United States
R01 AG018728 NIA NIH HHS United States
R01 CA165001 NCI NIH HHS United States
R01 GM053275 NIGMS NIH HHS United States
R01 HD042157 NICHD NIH HHS United States
R01 HL059367 NHLBI NIH HHS United States
R01 HL086694 NHLBI NIH HHS United States
R01 HL087641 NHLBI NIH HHS United States
R01 HL087679 NHLBI NIH HHS United States
R01 HL088119 NHLBI NIH HHS United States
R01 HL103866 NHLBI NIH HHS United States
R01 HL103931 NHLBI NIH HHS United States
R01 LM010098 NLM NIH HHS United States
R01 MH081802 NIMH NIH HHS United States
RG/09/012/28096 British Heart Foundation United Kingdom
RL1 MH083268 NIMH NIH HHS United States
U01 GM074518 NIGMS NIH HHS United States
U01 HG004402 NHGRI NIH HHS United States
U01 HL072515 NHLBI NIH HHS United States
U01 HL084756 NHLBI NIH HHS United States
U24 MH068457 NIMH NIH HHS United States
U54 RR020278 NCRR NIH HHS United States
UL1 RR025005 NCRR NIH HHS United States
UL1 TR000439 NCATS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Animals
Cell Cycle genetics
Cytokines metabolism
Drosophila melanogaster genetics
Erythrocytes metabolism
Female metabolism
Gene Expression Regulation genetics
Genetic Loci genetics
Genome-Wide Association Study genetics
Hematopoiesis genetics
Hemoglobins genetics
Humans genetics
Male genetics
Mice genetics
Organ Specificity genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
RNA Interference genetics
Signal Transduction genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cytokines
0 Hemoglobins
OTHER ID's
OTHERID SOURCE
NIHMS447872 NLM
PMC3623669 NLM