Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans

被引：59

作者：

Schick, Ursula M. ^{[1
,2
,3
]}

Jain, Deepti ^{[4
]}

Hodonsky, Chani J. ^{[5
]}

Morrison, Jean V. ^{[4
]}

Davis, James P. ^{[6
]}

Brown, Lisa ^{[4
]}

Sofer, Tamar ^{[4
]}

Conomos, Matthew P. ^{[4
]}

Schurmann, Claudia ^{[2
,3
]}

McHugh, Caitlin P. ^{[4
]}

Nelson, Sarah C. ^{[4
]}

Vadlamudi, Swarooparani ^{[6
]}

Stilp, Adrienne ^{[4
]}

Plantinga, Anna ^{[4
]}

Baier, Leslie ^{[7
]}

Bien, Stephanie A. ^{[1
]}

Gogarten, Stephanie M. ^{[4
]}

Laurie, Cecelia A. ^{[4
]}

Taylor, Kent D. ^{[8
,9
]}

Liu, Yongmei ^{[10
]}

Auer, Paul L. ^{[11
]}

Franceschini, Nora ^{[5
]}

Szpiro, Adam ^{[4
]}

Rice, Ken ^{[4
]}

Kerr, Kathleen F. ^{[4
]}

Rotter, Jerome I. ^{[8
]}

Hanson, Robert L. ^{[7
]}

Papanicolaou, George ^{[12
]}

Rich, Stephen S. ^{[13
,14
]}

Loos, Ruth J. F. ^{[2
,3
,15
]}

Browning, Brian L. ^{[4
]}

Browning, Sharon R. ^{[4
]}

Weir, Bruce S. ^{[4
]}

Laurie, Cathy C. ^{[4
]}

Mohlke, Karen L. ^{[6
]}

North, Kari E. ^{[5
]}

Thornton, Timothy A. ^{[4
]}

Reiner, Alex P. ^{[1
]}

机构：

[1] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA

[2] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA

[4] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[5] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA

[6] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[7] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, 445 North 5th St, Phoenix, AZ 85004 USA

[8] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA

[9] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Torrance, CA 90502 USA

[10] Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA

[11] Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA

[12] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA

[13] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA

[14] Univ Virginia, Dept Med, Div Endocrinol, Charlottesville, VA 22908 USA

[15] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2016年 / 98卷 / 02期

关键词：

TRANSCRIPTION FACTOR; GENETIC-VARIATION; AFRICAN-AMERICAN; SEQUENCE; THROMBOCYTOPENIA; MUTATIONS; INFERENCE; BINDING; DESIGN; ETV6;

D O I：

10.1016/j.ajhg.2015.12.003

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 x 10 (28)) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits.

引用

页码：229 / 242

页数：14

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