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

Ursula M Schick; Deepti Jain; Chani J Hodonsky; Jean V Morrison; James P Davis; Lisa Brown; Tamar Sofer; Matthew P Conomos; Claudia Schurmann; Caitlin P McHugh; Sarah C Nelson; Swarooparani Vadlamudi; Adrienne Stilp; Anna Plantinga; Leslie Baier; Stephanie A Bien; Stephanie M Gogarten; Cecelia A Laurie; Kent D Taylor; Yongmei Liu; Paul L Auer; Nora Franceschini; Adam Szpiro; Ken Rice; Kathleen F Kerr; Jerome I Rotter; Robert L Hanson; George Papanicolaou; Stephen S Rich; Ruth J F Loos; Brian L Browning; Sharon R Browning; Bruce S Weir; Cathy C Laurie; Karen L Mohlke; Kari E North; Timothy A Thornton; Alex P Reiner

doi:10.1016/j.ajhg.2015.12.003

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

Am J Hum Genet. 2016 Feb 4;98(2):229-42. doi: 10.1016/j.ajhg.2015.12.003. Epub 2016 Jan 21.

Authors

Ursula M Schick¹, Deepti Jain², Chani J Hodonsky³, Jean V Morrison², James P Davis⁴, Lisa Brown², Tamar Sofer², Matthew P Conomos², Claudia Schurmann⁵, Caitlin P McHugh², Sarah C Nelson², Swarooparani Vadlamudi⁴, Adrienne Stilp², Anna Plantinga², Leslie Baier⁶, Stephanie A Bien⁷, Stephanie M Gogarten², Cecelia A Laurie², Kent D Taylor⁸, Yongmei Liu⁹, Paul L Auer¹⁰, Nora Franceschini³, Adam Szpiro², Ken Rice², Kathleen F Kerr², Jerome I Rotter¹¹, Robert L Hanson⁶, George Papanicolaou¹², Stephen S Rich¹³, Ruth J F Loos¹⁴, Brian L Browning², Sharon R Browning², Bruce S Weir², Cathy C Laurie², Karen L Mohlke⁴, Kari E North³, Timothy A Thornton², Alex P Reiner¹⁵

Affiliations

¹ 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.
² Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
³ Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA.
⁴ Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵ 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.
⁶ 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.
⁷ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA.
⁸ 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.
⁹ School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
¹⁰ Joseph J. Zilber School of Public Health, University of Wisconsin Milwaukee, Milwaukee, WI 53201, USA.
¹¹ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
¹² Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
¹³ 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.
¹⁴ 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.
¹⁵ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA. Electronic address: apreiner@uw.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Actinin / genetics
Adolescent
Adult
Aged
Alleles
Gene Frequency
Genetic Association Studies / methods*
Genetic Loci*
Genotype
Genotyping Techniques
Hispanic or Latino / genetics*
Humans
MEF2 Transcription Factors / genetics
Membrane Proteins / genetics
Middle Aged
Phenotype
Platelet Count*
Polymorphism, Single Nucleotide
Receptors, GABA-B / genetics
Young Adult

Substances

ACTN1 protein, human
MEF2 Transcription Factors
MEF2C protein, human
Membrane Proteins
Receptors, GABA-B
SRPX protein, human
Actinin

Abstract

Publication types

MeSH terms

Substances

Grants and funding