title: Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans.
abstract: 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 × 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.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Ursula M
authors.initials: UM
authors.lastname: Schick
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Deepti
authors.initials: D
authors.lastname: Jain
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA.
authors.forename: Chani J
authors.initials: CJ
authors.lastname: Hodonsky
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jean V
authors.initials: JV
authors.lastname: Morrison
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Davis
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Brown
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sofer
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Conomos
authors.affiliation: Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schurmann
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Caitlin P
authors.initials: CP
authors.lastname: McHugh
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Nelson
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Swarooparani
authors.initials: S
authors.lastname: Vadlamudi
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Stilp
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Plantinga
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, NIH, 445 North 5(th) Street, Phoenix, AZ 85004, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Baier
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Bien
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Gogarten
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Cecelia A
authors.initials: CA
authors.lastname: Laurie
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA; Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.affiliation: School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Joseph J. Zilber School of Public Health, University of Wisconsin Milwaukee, Milwaukee, WI 53201, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Auer
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Szpiro
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Rice
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, NIH, 445 North 5(th) Street, Phoenix, AZ 85004, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.affiliation: Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: George
authors.initials: G
authors.lastname: Papanicolaou
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Division of Endocrinology, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Browning
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Browning
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Weir
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA.
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Thornton
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA. Electronic address: apreiner@uw.edu.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Reiner
mesh_terms: D000185:Actinin / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods*; D056426:Genetic Loci; D005838:Genotype; D060005:Genotyping Techniques; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D018080:Receptors, GABA-B / Q000235:genetics; D055815:Young Adult
chemical_list: C526905:ACTN1 protein, human; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D008565:Membrane Proteins; D018080:Receptors, GABA-B; C486297:SRPX protein, human; D000185:Actinin