Human Molecular Genetics Advance Access published online on February 19, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh091
© 2004 by Oxford University Press
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1 Program for Population Genetics, Harvard School of Public Health, Boston, MA USA
* To whom correspondence should be addressed. E-mail: xu{at}hsph.harvard.edu.
Preterm delivery (PTD) is the leading cause of infant mortality and morbidity worldwide. The etiology of PTD is largely unknown but is believed to be complex, encompassing multiple genetic and environmental determinants. To date, reports of genetic studies on PTD are sparse. We conducted a large-scale case-control study exploring the associations of 426 single-nucleotide polymorphisms (SNPs) with PTD in 300 mothers with PTD and 458 mothers with term deliveries at the Boston Medical Center. 25 candidate genes were finally included in the haplotype analysis, and a significant association of F5 gene haplotype with PTD was revealed and it remained significant after Bonferroni correction for multiple testing (p=0.025). We applied different statistical algorithms (both Gibbs sampling and expectation-maximization) in reconstructing haplotype phases and different tests (both likelihood ratio test and permutation test) in association analyses, and all yielded similar results. We also performed exploratory ethnicity-specific analyses, which confirmed the consistent findings of the F5 gene across the ethnic groups. Moreover, IL1R2 (p=0.002 in Blacks), NOS2A (p<0.001 in Whites) and OPRM1 (p=0.004 in Hispanics) gene haplotypes were associated with PTD in specific ethnic group but not at global significance level. In summary, our results underscore the potentially important role of F5 gene variants in the pathogenesis of PTD, and demonstrate the utility of high-throughput genotyping and haplotype-based approach in dissecting genetic basis of complex traits.
Article
A Large-Scale Candidate Gene Association Study on Preterm Delivery: Application of High-Throughput Genotyping Technology and Advanced Statistical Methods
2 Department of Pediatrics, Boston University Medical Center, Boston, MA; and the Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital, Chicago, IL, USA
3 Program for Population Genetics, Harvard School of Public Health, Boston, MA USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA USA
4 Department of Biostatistics, Harvard School of Public Health, Boston, MA USA
5 Program for Population Genetics, Harvard School of Public Health, 665 Huntington Ave. FXB101, Boston, MA 02115, USA
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