Journal article
Investigation of genetic risk factors for chronic adult diseases for association with preterm birth
Human genetics, Vol.132(1), pp.57-67
01/2013
DOI: 10.1007/s00439-012-1223-x
PMCID: PMC3864772
PMID: 22972380
Abstract
Preterm birth (PTB) is the leading cause of infant mortality. PTB pathophysiology overlaps with those of adult cardiovascular, immune and metabolic disorders (CIMD), with mechanisms including inflammation, immunotolerance, thrombosis, and nutrient metabolism. Whereas many genetic factors for CIMD have been identified, progress in PTB has lagged. We hypothesized that highly validated genetic risk factors for CIMD may also be associated with PTB. We conducted case–control study of four female cohorts with spontaneous PTB (n = 673) versus term (n = 1119). Of 35 SNPs genotyped, there were 13 statistically significant associations (P<0.05), which were more than expected (binomial test; P = 0.02). In US White (307 cases/342 controls), the G allele of HLA-DQA1 (A/G) rs9272346 was protective for PTBin the initial discovery cohort (P = 0.02; OR = 0.65; 95 % CI 0.46, 0.94). This protective association replicated (P = 0.02; OR = 0.85; 95 % CI 0.75, 0.97) nominally in the Danish Cohort (883 cases, 959 controls), but lost significance upon multiple testing correction. We observed more statistically significant associations than expected, suggesting that chance is an unlikely explanation for one or more of the associations. Particularly, a protective association of the G allele of HLA-DQA1 was found in two independent cohorts, and in previous studies, this same allele was found to protect against type-1-diabetes (meta-analysis P value 5.52 × 10
−219
). Previous investigations have implicated HLA phenotypic variation in recurrent fetal loss and in chronic chorioamnionitis. Given the limited sample size in his study, we suggest larger studies to further investigate possible HLA genetic involvement in PTB.
Details
- Title: Subtitle
- Investigation of genetic risk factors for chronic adult diseases for association with preterm birth
- Creators
- Nadia Falah - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TNJude McElroy - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TNVictoria Snegovskikh - Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CTCharles J Lockwood - Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CTErrol Norwitz - Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CTJeffey C Murray - Department of Pediatrics, University of IowaEdward Kuczynski - Biology and Biochemistry Department, University of Houston, TXRamkumar Menon - Department of Obstetrics and Gynecology, University of Texas, Galveston, TXKari Teramo - Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, FinlandLouis J Muglia - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TNThomas Morgan - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.132(1), pp.57-67
- DOI
- 10.1007/s00439-012-1223-x
- PMID
- 22972380
- PMCID
- PMC3864772
- NLM abbreviation
- Hum Genet
- ISSN
- 0340-6717
- eISSN
- 1432-1203
- Grant note
- U01 HG004446 || HG / National Human Genome Research Institute : NHGRI U01 HG004438 || HG / National Human Genome Research Institute : NHGRI HHSN268200782096C || HG / National Human Genome Research Institute : NHGRI U01 HG004423 || HG / National Human Genome Research Institute : NHGRI
- Language
- English
- Date published
- 01/2013
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Family and Community Medicine; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025354702771
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