HHS Public Access Author manuscript Author Manuscript
Arch Dis Child Fetal Neonatal Ed. Author manuscript; available in PMC 2017 September 01. Published in final edited form as:
Arch Dis Child Fetal Neonatal Ed. 2017 September ; 102(5): F439–F445. doi:10.1136/ archdischild-2016-311545.
Genome Wide Association Study of Sepsis in Extremely Premature Infants
Author Manuscript
Lakshmi Srinivasan, MBBS, MTR1, Grier Page, PhD2, Haresh Kirpalani, BM, MSc1, Jeffrey C. Murray, MD3, Abhik Das, PhD4, Rosemary D. Higgins, MD5, Waldemar A. Carlo, MD6, Edward F. Bell, MD3, Ronald N. Goldberg, MD7, Kurt Schibler, MD8, Beena G. Sood, MD, MS9, David K. Stevenson, MD10, Barbara J. Stoll, MD11, Krisa P. Van Meurs, MD10, Karen J. Johnson, RN3, Joshua Levy, MS2, Scott A. McDonald, BS2, Kristin M. Zaterka-Baxter, RN, BSN2, Kathleen A. Kennedy, MD, MPH12, Pablo J. Sánchez, MD13, Shahnaz Duara, MD14, Michele C. Walsh, MD, MS15, Seetha Shankaran, MD16, James L. Wynn, MD17, and C. Michael Cotten, MD, MHS7 for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network 1Department
of Pediatrics, The Children’s Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, PA
2Social,
Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park,
NC 3University
Author Manuscript
4Social,
of Iowa, Department of Pediatrics, Iowa City, IA
Statistical and Environmental Sciences Unit, RTI International, Rockville, MD
5Eunice
Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 6Department
of Pediatrics, University of Alabama at Birmingham, Birmingham, AL
7Department
of Pediatrics, Duke University, Durham, NC
8Department
of Pediatrics, University of Cincinnati, Cincinnati, OH
9Department
of Pediatrics, Wayne State University, Detroit, MI
10Department
of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children’s Hospital, Palo Alto, CA
Author Manuscript
11Emory
University School of Medicine, Department of Pediatrics, Children’s Healthcare of Atlanta, Atlanta, GA 12Department
of Pediatrics, University of Texas Medical School at Houston, Houston, TX
13Department
of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX
Contact information for the corresponding author (and reprint request author): Lakshmi Srinivasan, MBBS MTR, Clinical Associate in Pediatrics, The Children’s Hospital of Philadelphia, Room 2NW17, 34th and Civic Center Boulevard, Philadelphia, PA 19104, [email protected], Phone: 215-590-1653, Fax: 215-590-3051. CONFLICTS OF INTEREST STATEMENT: The authors do not have any conflicts of interest to report.
Srinivasan et al.
Page 2
14University
of Miami Miller School of Medicine, Miami, FL
Author Manuscript
15Department
of Pediatrics, Rainbow Babies & Children’s Hospital, Case Western Reserve University, Cleveland, OH
16Department
of Pediatrics, Wayne State University, Detroit, MI
17Department
of Pediatrics, University of Florida, Gainesville, FL
Abstract Objective—To identify genetic variants associated with sepsis (early and late-onset) using a genome wide association (GWA) analysis in a cohort of extremely premature infants.
Author Manuscript
Study Design—Previously generated GWA data from the Neonatal Research Network’s anonymized genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole genome amplified DNA was genotyped for 1.2 million single nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. P values and false discovery rates were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p
Arch Dis Child Fetal Neonatal Ed. Author manuscript; available in PMC 2017 September 01. Published in final edited form as:
Arch Dis Child Fetal Neonatal Ed. 2017 September ; 102(5): F439–F445. doi:10.1136/ archdischild-2016-311545.
Genome Wide Association Study of Sepsis in Extremely Premature Infants
Author Manuscript
Lakshmi Srinivasan, MBBS, MTR1, Grier Page, PhD2, Haresh Kirpalani, BM, MSc1, Jeffrey C. Murray, MD3, Abhik Das, PhD4, Rosemary D. Higgins, MD5, Waldemar A. Carlo, MD6, Edward F. Bell, MD3, Ronald N. Goldberg, MD7, Kurt Schibler, MD8, Beena G. Sood, MD, MS9, David K. Stevenson, MD10, Barbara J. Stoll, MD11, Krisa P. Van Meurs, MD10, Karen J. Johnson, RN3, Joshua Levy, MS2, Scott A. McDonald, BS2, Kristin M. Zaterka-Baxter, RN, BSN2, Kathleen A. Kennedy, MD, MPH12, Pablo J. Sánchez, MD13, Shahnaz Duara, MD14, Michele C. Walsh, MD, MS15, Seetha Shankaran, MD16, James L. Wynn, MD17, and C. Michael Cotten, MD, MHS7 for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network 1Department
of Pediatrics, The Children’s Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, PA
2Social,
Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park,
NC 3University
Author Manuscript
4Social,
of Iowa, Department of Pediatrics, Iowa City, IA
Statistical and Environmental Sciences Unit, RTI International, Rockville, MD
5Eunice
Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 6Department
of Pediatrics, University of Alabama at Birmingham, Birmingham, AL
7Department
of Pediatrics, Duke University, Durham, NC
8Department
of Pediatrics, University of Cincinnati, Cincinnati, OH
9Department
of Pediatrics, Wayne State University, Detroit, MI
10Department
of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children’s Hospital, Palo Alto, CA
Author Manuscript
11Emory
University School of Medicine, Department of Pediatrics, Children’s Healthcare of Atlanta, Atlanta, GA 12Department
of Pediatrics, University of Texas Medical School at Houston, Houston, TX
13Department
of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX
Contact information for the corresponding author (and reprint request author): Lakshmi Srinivasan, MBBS MTR, Clinical Associate in Pediatrics, The Children’s Hospital of Philadelphia, Room 2NW17, 34th and Civic Center Boulevard, Philadelphia, PA 19104, [email protected], Phone: 215-590-1653, Fax: 215-590-3051. CONFLICTS OF INTEREST STATEMENT: The authors do not have any conflicts of interest to report.
Srinivasan et al.
Page 2
14University
of Miami Miller School of Medicine, Miami, FL
Author Manuscript
15Department
of Pediatrics, Rainbow Babies & Children’s Hospital, Case Western Reserve University, Cleveland, OH
16Department
of Pediatrics, Wayne State University, Detroit, MI
17Department
of Pediatrics, University of Florida, Gainesville, FL
Abstract Objective—To identify genetic variants associated with sepsis (early and late-onset) using a genome wide association (GWA) analysis in a cohort of extremely premature infants.
Author Manuscript
Study Design—Previously generated GWA data from the Neonatal Research Network’s anonymized genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole genome amplified DNA was genotyped for 1.2 million single nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. P values and false discovery rates were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p
