Journal article
Maternal coding variants in complement receptor 1 and spontaneous idiopathic preterm birth
Human genetics, Vol.132(8), pp.935-942
08/2013
DOI: 10.1007/s00439-013-1304-5
PMCID: PMC3868364
PMID: 23591632
Abstract
Preterm birth (PTB) is a major global public health concern. However, little is known about the pathophysiology of spontaneous idiopathic PTB. We tested the hypothesis that rare variants in families would target specific genes and pathways that contribute to PTB risk in the general population. Whole-exome sequencing was performed on 10 PTB mothers from densely affected families including two mother–daughter pairs. We identified novel variants shared between the two mother–daughter pairs when compared to a 1000 Genomes Project background exome file and investigated these genes for pathway aggregation using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Genes in enriched pathways were then surveyed in the other six PTB exomes and tested for association in a larger number of nuclear families. The KEGG complement and coagulation cascade was one of the most enriched pathways in our two mother–daughter pairs. When the six genes found in this pathway (CFH, CR1, F13B, F5, CR2, and C4BPA) were examined for novel missense variants, half of all the exomes harbored at least one. Association analysis of variants in these six gene regions in nuclear families from Finland (237 cases and 328 controls) found statistically significant associations after multiple test corrections in three CR1 SNPs; the strongest in an exonic missense SNP, rs6691117, p value = 6.91e−5, OR = 1.71. Our results demonstrate the importance of the complement and coagulation cascades in the pathophysiology of PTB, and suggest potential screening and intervention approaches to prevent prematurity that target this pathway.
Details
- Title: Subtitle
- Maternal coding variants in complement receptor 1 and spontaneous idiopathic preterm birth
- Creators
- Jude McElroy - Medical Scientist Training Program Vanderbilt University School of Medicine Nashville TN USACourtney Gutman - Division of Neonatology Vanderbilt University School of Medicine and Monroe Carell Jr. Children’s Hospital at Vanderbilt Nashville TN USAChristian Shaffer - Genome Technology Core Vanderbilt University Nashville TN USATamara Busch - Department of Pediatrics University of Iowa Carver College of Medicine Iowa IA USAHilkka Puttonen - Department of Obstetrics and Gynecology University Central Hospital Helsinki FinlandKari Teramo - Department of Obstetrics and Gynecology University Central Hospital Helsinki FinlandJeffrey Murray - Department of Pediatrics University of Iowa Carver College of Medicine Iowa IA USAMikko Hallman - Department of Pediatrics, Institute of Clinical Medicine University of Oulu Oulu FinlandLouis Muglia - Perinatal Institute Cincinnati Children’s Hospital Medical Center Cincinnati OH USA
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.132(8), pp.935-942
- DOI
- 10.1007/s00439-013-1304-5
- PMID
- 23591632
- PMCID
- PMC3868364
- NLM abbreviation
- Hum Genet
- ISSN
- 0340-6717
- eISSN
- 1432-1203
- Publisher
- Springer Berlin Heidelberg; Berlin/Heidelberg
- Language
- English
- Date published
- 08/2013
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025468702771
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