GWAS of Preterm Birth

Preterm birth (PTB, born before 37 weeks of gestation) is a leading cause of neonatal mortality and post-natal morbidity. PTB affects one in nine all live births in the U.S. Notably, the highest rate of PTB occurs among African Americans (one in six). PTB is a complex trait, likely determined by multiple environmental and genetic factors and their interactions. We demonstrated strong familial aggregation of preterm and low birthweight in the US Blacks and Whites (Wang et al, NEJM, 1995) and conducted the largest candidate gene study of preterm birth at that time (Hao et al, HMG, 2004). We showed that a subset of mothers with certain metabolic gene variants are particularly vulnerable to the adverse effects of cigarette smoking on low birthweight and preterm births (Wang et al, JAMA, 2002). We also published a number of papers that examined the effect of maternal pre-pregnancy BMI, micronutrient status, stress and environmental toxins on the risk of preterm birth and related conditions. This project, supported by a grant from the NICHD (2R01HD41702, PI, Xiaobin Wang), aimed to conduct a genome-wide association study (GWAS) and apply advanced statistical methods to identify susceptibility loci of PTB in a predominantly urban low-income African American sample, a subset of the Boston Birth Cohort. PUBLIC HEALTH REVELANCE: We anticipate that this study will lead to the identification of novel genetic loci of PTB and gene-environment interactions. Such findings not only will provide important insights into mechanisms leading to PTB, but also may help identify women at high-risk of PTB, which in turn, may lead to the development of early and targeted interventions that can prevent PTB or mitigate the severity and consequences of PTB.]]>
Criteria for cases A. Inclusion: All mothers who delivered preterm babies (<37 weeks of gestation, regardless of birthweight) at Boston Medical Center (BMC) were eligible as cases for the study. B. Exclusion: We excluded pregnancies as a result of in vitro fertilization or multiple gestation, and fetuses with chromosomal abnormalities or major birth defects. Additional exclusion criteria include mothers with congenital or acquired uterus lesions or with a known history of incompetent cervix, and preterm births due to maternal trauma (e.g., car accident). Criteria for controls Those mothers who delivered term (>37 weeks of gestation) babies at BMC and frequency matched with case mothers on race, age (± 5 years), baby's gender and parity were eligible as controls for this GWAS.]]>
The parent population for this GWAS is the Boston Birth Cohort (BBC), which was initiated by Dr. Xiaobin Wang in 1998 at the Boston Medical Center with the support of Dr. Barry Zuckerman, the former Chairman of the Department of Pediatrics and the Joel Alpert faculty development award by the Department of Pediatrics, Boston Medical Center. Subsequently, the Boston Birth Cohort was supported by multiple sources of funding, the March of Dimes Birth Defects Foundation (20-FY98-0701, 20-FY02-56 and #21-FY07-605, PI: Xiaobin Wang); and the National Institutes of Environmental Health Sciences (R21 ES011666, PI: Xiaobin Wang), and Eunice Kennedy Shriver National Institute of Child Health and Human Development (2R01HD41702, PI: Xiaobin Wang). We are indebted to many individuals who have contributed to the parent study and/or this GWAS of preterm birth, including Barry Zuckerman, Howard Bauchner, Colleen Pearson, Deanna Caruso, Xiumei Hong, Guoying Wang, Xin Liu, Hui-Ju Tsai, Nan Laird, L-J Wei, Louise Ryan, Jerry Klein, Phillip Stubblefield, Linda Heffner, Milton Kotelchuck, Michael Corwin, Paul Wise, Michael Kramer, Gary Kaufman, John Kasznica, Sandra Cerda, Daniel Weeks, Yunxian Yu, Shanchun Zhang, Fengxiu Ouyang, Lingling Fu, Natalie Cruz, Shannon Kiang, Katherin Ortiz, Maria Kroll, Monica Cintron, Xin Xu, Xiping Xu, Tim Niu, Ke Hao, Lin Wang, Xin Chen, Scott Venners, Lester Arguelles, Karen Mestan, Nana Matoba, Jessica L Schanta, Marie Jean, Max Paillaint, Kathleen Delmas, Emault Louis, Alison Little, Yohanna Mendez, Munish Gupta, Joel Sawadi, Claire Joseph, Anthony Bonzagni, Stephanie Apollon, Laurie Natale, Peters Otlans, Patricia Francisco, Jhenane Joseph, Jared Berkowitz, Maggie Francis, Rachel Sajous, Guang Li, Ang Li, Qing Wang, Schubert Bijous, Maria Eguez, Weili Chang, Ivan Villon, Roberto Beltran, Kimberlee Bulger, Nahomy Calixte, Ivette Martinez, Winnie Mei, Kristin McPhillips, Mathis Bauchner, Ann Ramsey, Douglas Rockwell, Zhu Chen, Yuelong Ji, Kristin Schwartz, Anastacia Wahl, Hilena Addis, Bolanle Ajao, Liliana Burdea, Elisabeth Carrigg, Ifta Choiriyyah, Mallory Clifford, Monica D'Ambrogi, Jane Daniels, Christopher DeEspinosa, Rebeca Diaz-Reyes, Rajelin Escondo, Emily Frankis, Emily Hu, Sato Kakihara, Anna Kropornicka, Suegene Lee, Anne Lilly, Samantha Margaritas, Molly McGlone, Miriam Million, Kyla Mor, Christiana Obeng, Anita Patel, Samantha Pollack, Yaritza Rodriguez, Edna Romero, Larisa Smith, Xuan Zhang, Marcela Ziemianski. We are particularly indebted to the nursing staff of Labor and Delivery at the Boston Medical Center for their long-standing assistance in data collection. We are grateful for the generous help and support of all of the Boston Medical Center participating mothers.]]>