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Nat Commun. 2017 Jun 9;8:15608. doi: 10.1038/ncomms15608.

Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth.

Author information

1
Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
2
Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
3
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health Baltimore, Maryland 21205, USA.
4
Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
5
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan 35053, Taiwan.
6
Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
7
Integrated Research Center for Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
8
Mary Ann &J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann &Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA.
9
Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118, USA.
10
Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
11
Department of Pathology and Laboratory Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
12
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
13
Department of Mental Health, Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
14
Department of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
15
Division of General Pediatrics &Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Abstract

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such 'missing heritability' may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10-8; empirical PG × E=1.2 × 10-8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10-9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.

PMID:
28598419
PMCID:
PMC5472707
DOI:
10.1038/ncomms15608
[Indexed for MEDLINE]
Free PMC Article

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