Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.;Kanazawa Univ, Div Cardiovasc Med, Grad Sch Med Sci, Kanazawa, Ishikawa 9200942, Japan.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
Chen, Ming-Huei (författare)
NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.
Yanek, Lisa R. (författare)
Johns Hopkins Univ, Div Gen Internal Med, Dept Med, Sch Med, Baltimore, MD 21205 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.
Slater, Andrew J. (författare)
GlaxoSmithKline, Genet, Target Sci, Res Triangle Pk, NC 27709 USA.;OmicSoft Corp, Cary, NC 27513 USA.
Pankratz, Nathan (författare)
Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA.
Polfus, Linda (författare)
Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
Schurmann, Claudia (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.
Giri, Ayush (författare)
Vanderbilt Univ, Inst Med & Publ Hlth, Div Epidemiol, Nashville, TN 37235 USA.
Brody, Jennifer A. (författare)
Univ Washington, Dept Med, Seattle, WA 98101 USA.
Lange, Leslie A. (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.
Manichaikul, Ani (författare)
Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA.
Univ Washington, Dept Genome Sci, Seattle, WA 98105 USA.
Raffield, Laura M. (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.
Quarells, Rakale (författare)
Morehouse Sch Med, Social Epidemiol Res Ctr, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
Willer, Cristen J. (författare)
Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48108 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Dept Human Genet, Ann Arbor, MI 48108 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI 48108 USA.
Peloso, Gina M. (författare)
Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA.
Abecasis, Goncalo R. (författare)
Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48108 USA.
Liu, Dajiang J. (författare)
Penn State Univ Hosp, Dept Publ Hlth Sci, Coll Med, Hershey, PA 17033 USA.
Deloukas, Panos (författare)
Queen Mary Univ London, William Harvey Res Inst, London E1 4NS, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia.
Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA.
Waterworth, Dawn M. (författare)
GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA 19406 USA.
Wallentin, Lars (författare)
Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)
White, Harvey D. (författare)
Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.;Univ Auckland, Auckland 1142, New Zealand.
Floyd, James S. (författare)
Univ Washington, Dept Med, Seattle, WA 98101 USA.
Bartz, Traci M. (författare)
Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
Rice, Kenneth M. (författare)
Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
Psaty, Bruce M. (författare)
Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
Vanderbilt Univ, Inst Med & Publ Hlth, Div Epidemiol, Nashville, TN 37235 USA.
Ganesh, Santhi K. (författare)
Univ Michigan, Dept Internal & Human Genet, Ann Arbor, MI 48108 USA.
Kathiresan, Sekar (författare)
Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
Faraday, Nauder (författare)
Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
Auer, Paul L. (författare)
Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
Reiner, Alex P. (författare)
Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
Lettre, Guillaume (författare)
Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
Johnson, Andrew D. (författare)
NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common(ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV(PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
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)