Imperial College London

DrAbbasDehghan

Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

157Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tajuddin:2016:10.1016/j.ajhg.2016.05.003,
author = {Tajuddin, SM and Schick, UM and Eicher, JD and Chami, N and Giri, A and Brody, JA and Hill, WD and Kacprowski, T and Li, J and Lyytikäinen, LP and Manichaikul, A and Mihailov, E and O'Donoghue, ML and Pankratz, N and Pazoki, R and Polfus, LM and Smith, AV and Schurmann, C and Vacchi-Suzzi, C and Waterworth, DM and Evangelou, E and Yanek, LR and Burt, A and Chen, MH and van, Rooij FJ and Floyd, JS and Greinacher, A and Harris, TB and Highland, HM and Lange, LA and Liu, Y and Mägi, R and Nalls, MA and Mathias, RA and Nickerson, DA and Nikus, K and Starr, JM and Tardif, JC and Tzoulaki, I and Velez, Edwards DR and Wallentin, L and Bartz, TM and Becker, LC and Denny, JC and Raffield, LM and Rioux, JD and Friedrich, N and Fornage, M and Gao, H and Hirschhorn, JN and Liewald, DC and Rich, SS and Uitterlinden, A and Bastarache, L and Becker, DM and Boerwinkle, E and de, Denus S and Bottinger, EP and Hayward, C and Hofman, A and Homuth, G and Lange, E and Launer, LJ and Lehtimäki, T and Lu, Y },
doi = {10.1016/j.ajhg.2016.05.003},
journal = {American Journal of Human Genetics},
pages = {22--39},
title = {Large-scale exome-wide association analysis identifies loci for white blood cell traits and pleiotropy with immune-mediated diseases},
url = {http://dx.doi.org/10.1016/j.ajhg.2016.05.003},
volume = {99},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.
AU - Tajuddin,SM
AU - Schick,UM
AU - Eicher,JD
AU - Chami,N
AU - Giri,A
AU - Brody,JA
AU - Hill,WD
AU - Kacprowski,T
AU - Li,J
AU - Lyytikäinen,LP
AU - Manichaikul,A
AU - Mihailov,E
AU - O'Donoghue,ML
AU - Pankratz,N
AU - Pazoki,R
AU - Polfus,LM
AU - Smith,AV
AU - Schurmann,C
AU - Vacchi-Suzzi,C
AU - Waterworth,DM
AU - Evangelou,E
AU - Yanek,LR
AU - Burt,A
AU - Chen,MH
AU - van,Rooij FJ
AU - Floyd,JS
AU - Greinacher,A
AU - Harris,TB
AU - Highland,HM
AU - Lange,LA
AU - Liu,Y
AU - Mägi,R
AU - Nalls,MA
AU - Mathias,RA
AU - Nickerson,DA
AU - Nikus,K
AU - Starr,JM
AU - Tardif,JC
AU - Tzoulaki,I
AU - Velez,Edwards DR
AU - Wallentin,L
AU - Bartz,TM
AU - Becker,LC
AU - Denny,JC
AU - Raffield,LM
AU - Rioux,JD
AU - Friedrich,N
AU - Fornage,M
AU - Gao,H
AU - Hirschhorn,JN
AU - Liewald,DC
AU - Rich,SS
AU - Uitterlinden,A
AU - Bastarache,L
AU - Becker,DM
AU - Boerwinkle,E
AU - de,Denus S
AU - Bottinger,EP
AU - Hayward,C
AU - Hofman,A
AU - Homuth,G
AU - Lange,E
AU - Launer,LJ
AU - Lehtimäki,T
AU - Lu,Y
AU - Metspalu,A
AU - O'Donnell,CJ
AU - Quarells,RC
AU - Richard,M
AU - Torstenson,ES
AU - Taylor,KD
AU - Vergnaud,AC
AU - Zonderman,AB
AU - Crosslin,DR
AU - Deary,IJ
AU - Dörr,M
AU - Elliott,P
AU - Evans,MK
AU - Gudnason,V
AU - Kähönen,M
AU - Psaty,BM
AU - Rotter,JI
AU - Slater,AJ
AU - Dehghan,A
AU - White,HD
AU - Ganesh,SK
AU - Loos,RJ
AU - Esko,T
AU - Faraday,N
AU - Wilson,JG
AU - Cushman,M
AU - Johnson,AD
AU - Edwards,TL
AU - Zakai,NA
AU - Lettre,G
AU - Reiner,AP
AU - Auer,PL
DO - 10.1016/j.ajhg.2016.05.003
EP - 39
PY - 2016///
SN - 1537-6605
SP - 22
TI - Large-scale exome-wide association analysis identifies loci for white blood cell traits and pleiotropy with immune-mediated diseases
T2 - American Journal of Human Genetics
UR - http://dx.doi.org/10.1016/j.ajhg.2016.05.003
UR - http://www.ncbi.nlm.nih.gov/pubmed/27346689
UR - http://hdl.handle.net/10044/1/34581
VL - 99
ER -