TY - JOUR
T1 - Genome-wide association study identifies a novel maternal gene × stress interaction associated with spontaneous preterm birth
AU - Hong, Xiumei
AU - Surkan, Pamela J.
AU - Zhang, Boyang
AU - Keiser, Amaris
AU - Ji, Yuelong
AU - Ji, Hongkai
AU - Burd, Irina
AU - Bustamante-Helfrich, Blandine
AU - Ogunwole, S. Michelle
AU - Tang, Wan Yee
AU - Liu, Li
AU - Pearson, Colleen
AU - Cerda, Sandra
AU - Zuckerman, Barry
AU - Hao, Lingxin
AU - Wang, Xiaobin
N1 - Funding Information:
We thank all of the study participants in the BBC for supporting this study. We are also grateful for the dedication and hard work of the field team at the Department of Pediatrics, Boston University School of Medicine, and for the support of the obstetric nursing staff at Boston Medical Center. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University, contract numbers HSN268200782096C and HHSN268201200008I. The GWAS data cleaning was performed by Dr. Laurie and her team at Washington University following the GENEVA protocol. The authors thank Linda Rosen of the Boston University Clinical Data Warehouse for assistance in obtaining relevant clinical information; the Clinical Data Warehouse service is supported by Boston University Clinical and Translational Institute and the National Institutes of Health Clinical and Translational Science Award (grant U54-TR001012). This work is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; grant numbers include R03HD096136, R21HD085556, 2R01HD041702, R01HD086013 and HD098232) and the Johns Hopkins Population Center (NICHD R24HD042854). The Boston Birth Cohort (the parent study) is also supported in part by the Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services (HHS) grants (R40MC27443 and UJ2MC31074). This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by NIH, HRSA, HHS or the US Government.
Publisher Copyright:
© 2020, International Pediatric Research Foundation, Inc.
PY - 2021/5
Y1 - 2021/5
N2 - Background: Maternal stress is potentially a modifiable risk factor for spontaneous preterm birth (sPTB). However, epidemiologic findings on the maternal stress−sPTB relationship have been inconsistent. Methods: To investigate whether the maternal stress−sPTB associations may be modified by genetic susceptibility, we performed genome-wide gene × stress interaction analyses in 1490 African-American women from the Boston Birth cohort who delivered term (n = 1033) or preterm (n = 457) infants. Genotyping was performed using Illumina HumanOmni 2.5 array. Replication was performed using data from the NICHD genomic and Proteomic Network (GPN) for PTB research. Results: rs35331017, a T-allele insertion/deletion polymorphism in the protein-tyrosine phosphatase receptor Type D (PTPRD) gene, was the top hit that interacted significantly with maternal lifetime stress on risk of sPTB (PG × E = 4.7 × 10−8). We revealed a dose-responsive association between degree of stress and risk of sPTB in mothers carrying the insertion/insertion genotype, but an inverse association was observed in mothers carrying the heterozygous or deletion/deletion genotypes. This interaction was replicated in African-American (PG × E = 0.088) and Caucasian mothers (PG × E = 0.023) from the GPN study. Conclusion: We demonstrated a significant maternal PTPRD × stress interaction on sPTB risk. This finding, if further confirmed, may provide new insight into individual susceptibility to stress-induced sPTB. Impact: This was the first preterm study to demonstrate a significant genome-wide gene−stress interaction in African Americans, specifically, PTPRD gene variants can interact with maternal perceived stress to affect risk of spontaneous preterm birth.The PTPRD × maternal stress interaction was demonstrated in African Americans and replicated in both African Americans and Caucasians from the GPN study.Our findings highlight the importance of considering genetic susceptibility in assessing the role of maternal stress on spontaneous preterm birth.
AB - Background: Maternal stress is potentially a modifiable risk factor for spontaneous preterm birth (sPTB). However, epidemiologic findings on the maternal stress−sPTB relationship have been inconsistent. Methods: To investigate whether the maternal stress−sPTB associations may be modified by genetic susceptibility, we performed genome-wide gene × stress interaction analyses in 1490 African-American women from the Boston Birth cohort who delivered term (n = 1033) or preterm (n = 457) infants. Genotyping was performed using Illumina HumanOmni 2.5 array. Replication was performed using data from the NICHD genomic and Proteomic Network (GPN) for PTB research. Results: rs35331017, a T-allele insertion/deletion polymorphism in the protein-tyrosine phosphatase receptor Type D (PTPRD) gene, was the top hit that interacted significantly with maternal lifetime stress on risk of sPTB (PG × E = 4.7 × 10−8). We revealed a dose-responsive association between degree of stress and risk of sPTB in mothers carrying the insertion/insertion genotype, but an inverse association was observed in mothers carrying the heterozygous or deletion/deletion genotypes. This interaction was replicated in African-American (PG × E = 0.088) and Caucasian mothers (PG × E = 0.023) from the GPN study. Conclusion: We demonstrated a significant maternal PTPRD × stress interaction on sPTB risk. This finding, if further confirmed, may provide new insight into individual susceptibility to stress-induced sPTB. Impact: This was the first preterm study to demonstrate a significant genome-wide gene−stress interaction in African Americans, specifically, PTPRD gene variants can interact with maternal perceived stress to affect risk of spontaneous preterm birth.The PTPRD × maternal stress interaction was demonstrated in African Americans and replicated in both African Americans and Caucasians from the GPN study.Our findings highlight the importance of considering genetic susceptibility in assessing the role of maternal stress on spontaneous preterm birth.
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U2 - 10.1038/s41390-020-1093-1
DO - 10.1038/s41390-020-1093-1
M3 - Article
C2 - 32726798
AN - SCOPUS:85088792293
SN - 0031-3998
VL - 89
SP - 1549
EP - 1556
JO - Pediatric Research
JF - Pediatric Research
IS - 6
ER -