Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
Eicher, John D. (författare)
NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.
Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
Vacchi-Suzzi, Caterina (författare)
SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA.
Waterworth, Dawn M. (författare)
GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA 19406 USA.
Univ N Carolina, Dept Genet & Biostat, Chapel Hill, NC 27599 USA.
Launer, Lenore J. (författare)
NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
Lehtimaki, Terho (författare)
Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
Lu, Yingchang (författare)
Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
Metspalu, Andres (författare)
Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
O'Donnell, Chris J. (författare)
NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.;Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA 02118 USA.;Boston Vet Adm Healthcare, Ctr Populat Genom, Boston, MA 02118 USA.
Quarells, Rakale C. (författare)
Morehouse Sch Med, Social Epidemiol Res Ctr, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland.
Psaty, Bruce M. (författare)
Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
Rotter, Jerome I. (författare)
Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA.
Slater, Andrew J. (författare)
OmicSoft Corp, Cary, NC 27513 USA.;GlaxoSmithKline, Genet Target Sci, Res Triangle Pk, NC 27709 USA.
Dehghan, Abbas (författare)
Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.
White, Harvey D. (författare)
Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.;Univ Auckland, Auckland 1142, New Zealand.
Ganesh, Santhi K. (författare)
Univ Michigan, Dept Internal Med, Ann Arbor, MI 48108 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48108 USA.
Loos, Ruth J. F. (författare)
Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
Esko, Tonu (författare)
Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Faraday, Nauder (författare)
Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
Wilson, James G. (författare)
Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
Cushman, Mary (författare)
Univ Vermont, Dept Med, Div Hematol Oncol, Colchester, VT 05446 USA.
Johnson, Andrew D. (författare)
NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.
Edwards, Todd L. (författare)
Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Div Epidemiol,Dept Med, Nashville, TN 37203 USA.
Zakai, Neil A. (författare)
Univ Vermont, Dept Med, Div Hematol Oncol, Colchester, VT 05446 USA.
NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. (creator_code:org_t)
2016
2016
Engelska.
Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 99:1, s. 22-39
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 similar to 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.
Ämnesord
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)