Localization of a major susceptibility locus influencing preterm birth

G. Chittoor, V. S. Farook, S. Puppala, S. P. Fowler, J. Schneider, T. D. Dyer, S. A. Cole, J. L. Lynch, J. E. Curran, L. Almasy, J. W. MacCluer, A. G. Comuzzie, D. E. Hale, R. S. Ramamurthy, D. J. Dudley, E. K. Moses, R. Arya, D. M. Lehman, C. P. Jenkinson, B. S. BradshawR. A. DeFronzo, J. Blangero, R. Duggirala

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Pretermbirth (PTB) is a complex trait, but little is known regarding its major genetic determinants. The objective of this study is to localize genes that influence susceptibility toPTBinMexican Americans (MAs), a minority population in the USA, using predominantly microfilmed birth certificate-based data obtained from the San Antonio Family BirthWeight Study. Only 1302 singleton births from 288 families with information on PTB and significant covariateswere considered for genetic analysis. PTB is defined as a childbirth that occurs at <37 completed weeks of gestation, and the prevalence of PTB in this sample was 6.4%. An ~10 cM genetic map was used to conduct a genome-wide linkage analysis using the program SOLAR. The heritability of PTB was high (h2±SE: 0.75±0.20) and significant (P = 4.5 × 10-5), after adjusting for the significant effects of birthweight and birth order.We found significant evidence for linkage of PTB (LOD = 3.6; nominal P = 2.3 ×10-5; empirical P = 1.0× 1010-5) on chromosome 18q between markers D18S1364 and D18S541. Several other chromosomal regions (2q, 9p, 16q and 20q) were also potentially linked with PTB. A strong positional candidate gene in the 18q linked region is SERPINB2 or PAI-2, a member of the plasminogen activator system that is associated with various reproductive processes. In conclusion, to our knowledge, perhaps for the first time in MAs or US populations, we have localized a major susceptibility locus for PTB on chromosome 18q21.33-q23.

Original languageEnglish (US)
Article numbergat036
Pages (from-to)687-696
Number of pages10
JournalMolecular Human Reproduction
Volume19
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Premature Birth
Plasminogen Activator Inhibitor 2
Parturition
Birth Certificates
Chromosomes, Human, Pair 5
Birth Order
Plasminogen Activators
Population
Genes
Chromosomes
Genome
Pregnancy

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Embryology
  • Molecular Biology
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Cell Biology

Cite this

Chittoor, G., Farook, V. S., Puppala, S., Fowler, S. P., Schneider, J., Dyer, T. D., ... Duggirala, R. (2013). Localization of a major susceptibility locus influencing preterm birth. Molecular Human Reproduction, 19(10), 687-696. [gat036]. https://doi.org/10.1093/molehr/gat036
Chittoor, G. ; Farook, V. S. ; Puppala, S. ; Fowler, S. P. ; Schneider, J. ; Dyer, T. D. ; Cole, S. A. ; Lynch, J. L. ; Curran, J. E. ; Almasy, L. ; MacCluer, J. W. ; Comuzzie, A. G. ; Hale, D. E. ; Ramamurthy, R. S. ; Dudley, D. J. ; Moses, E. K. ; Arya, R. ; Lehman, D. M. ; Jenkinson, C. P. ; Bradshaw, B. S. ; DeFronzo, R. A. ; Blangero, J. ; Duggirala, R. / Localization of a major susceptibility locus influencing preterm birth. In: Molecular Human Reproduction. 2013 ; Vol. 19, No. 10. pp. 687-696.
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Chittoor, G, Farook, VS, Puppala, S, Fowler, SP, Schneider, J, Dyer, TD, Cole, SA, Lynch, JL, Curran, JE, Almasy, L, MacCluer, JW, Comuzzie, AG, Hale, DE, Ramamurthy, RS, Dudley, DJ, Moses, EK, Arya, R, Lehman, DM, Jenkinson, CP, Bradshaw, BS, DeFronzo, RA, Blangero, J & Duggirala, R 2013, 'Localization of a major susceptibility locus influencing preterm birth', Molecular Human Reproduction, vol. 19, no. 10, gat036, pp. 687-696. https://doi.org/10.1093/molehr/gat036

Localization of a major susceptibility locus influencing preterm birth. / Chittoor, G.; Farook, V. S.; Puppala, S.; Fowler, S. P.; Schneider, J.; Dyer, T. D.; Cole, S. A.; Lynch, J. L.; Curran, J. E.; Almasy, L.; MacCluer, J. W.; Comuzzie, A. G.; Hale, D. E.; Ramamurthy, R. S.; Dudley, D. J.; Moses, E. K.; Arya, R.; Lehman, D. M.; Jenkinson, C. P.; Bradshaw, B. S.; DeFronzo, R. A.; Blangero, J.; Duggirala, R.

In: Molecular Human Reproduction, Vol. 19, No. 10, gat036, 01.10.2013, p. 687-696.

Research output: Contribution to journalArticle

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T1 - Localization of a major susceptibility locus influencing preterm birth

AU - Chittoor, G.

AU - Farook, V. S.

AU - Puppala, S.

AU - Fowler, S. P.

AU - Schneider, J.

AU - Dyer, T. D.

AU - Cole, S. A.

AU - Lynch, J. L.

AU - Curran, J. E.

AU - Almasy, L.

AU - MacCluer, J. W.

AU - Comuzzie, A. G.

AU - Hale, D. E.

AU - Ramamurthy, R. S.

AU - Dudley, D. J.

AU - Moses, E. K.

AU - Arya, R.

AU - Lehman, D. M.

AU - Jenkinson, C. P.

AU - Bradshaw, B. S.

AU - DeFronzo, R. A.

AU - Blangero, J.

AU - Duggirala, R.

PY - 2013/10/1

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N2 - Pretermbirth (PTB) is a complex trait, but little is known regarding its major genetic determinants. The objective of this study is to localize genes that influence susceptibility toPTBinMexican Americans (MAs), a minority population in the USA, using predominantly microfilmed birth certificate-based data obtained from the San Antonio Family BirthWeight Study. Only 1302 singleton births from 288 families with information on PTB and significant covariateswere considered for genetic analysis. PTB is defined as a childbirth that occurs at <37 completed weeks of gestation, and the prevalence of PTB in this sample was 6.4%. An ~10 cM genetic map was used to conduct a genome-wide linkage analysis using the program SOLAR. The heritability of PTB was high (h2±SE: 0.75±0.20) and significant (P = 4.5 × 10-5), after adjusting for the significant effects of birthweight and birth order.We found significant evidence for linkage of PTB (LOD = 3.6; nominal P = 2.3 ×10-5; empirical P = 1.0× 1010-5) on chromosome 18q between markers D18S1364 and D18S541. Several other chromosomal regions (2q, 9p, 16q and 20q) were also potentially linked with PTB. A strong positional candidate gene in the 18q linked region is SERPINB2 or PAI-2, a member of the plasminogen activator system that is associated with various reproductive processes. In conclusion, to our knowledge, perhaps for the first time in MAs or US populations, we have localized a major susceptibility locus for PTB on chromosome 18q21.33-q23.

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Chittoor G, Farook VS, Puppala S, Fowler SP, Schneider J, Dyer TD et al. Localization of a major susceptibility locus influencing preterm birth. Molecular Human Reproduction. 2013 Oct 1;19(10):687-696. gat036. https://doi.org/10.1093/molehr/gat036