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. Bradshaw; R. A. DeFronzo; J. Blangero; R. Duggirala

doi:10.1093/molehr/gat036

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

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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× 10^10-5) 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 language	English (US)
Article number	gat036
Pages (from-to)	687-696
Number of pages	10
Journal	Molecular Human Reproduction
Volume	19
Issue number	10
DOIs	https://doi.org/10.1093/molehr/gat036
State	Published - Oct 2013

All Science Journal Classification (ASJC) codes

General Medicine

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10.1093/molehr/gat036

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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., ... Duggirala, R. (2013). Localization of a major susceptibility locus influencing preterm birth. Molecular Human Reproduction, 19(10), 687-696. Article gat036. https://doi.org/10.1093/molehr/gat036

@article{d36e06b558fc45bca6943efcd90b772e,

title = "Localization of a major susceptibility locus influencing preterm birth",

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.",

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

note = "Funding Information: This study was supported by grants from the National Institute of Health [HD041111, DK053889, DK042273, P01 HL045522, DK047482, MH059490 and M01-RR-01346]. In addition, this work was supported by a Veterans Administration Epidemiologic grant. The AT&T Genomics Computing Center supercomputing facilities used for this work were supported in part by a gift from the AT&T Foundation and with support from the National Center for Research Resources Grant Number S10 RR029392. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program grants C06 RR013556 and C06 RR017515 from the National Center for Research Resources of the National Institutes of Health.",

year = "2013",

month = oct,

doi = "10.1093/molehr/gat036",

language = "English (US)",

volume = "19",

pages = "687--696",

journal = "Molecular Human Reproduction",

issn = "1360-9947",

publisher = "Oxford University Press",

number = "10",

}

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

TY - JOUR

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.

N1 - Funding Information: This study was supported by grants from the National Institute of Health [HD041111, DK053889, DK042273, P01 HL045522, DK047482, MH059490 and M01-RR-01346]. In addition, this work was supported by a Veterans Administration Epidemiologic grant. The AT&T Genomics Computing Center supercomputing facilities used for this work were supported in part by a gift from the AT&T Foundation and with support from the National Center for Research Resources Grant Number S10 RR029392. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program grants C06 RR013556 and C06 RR017515 from the National Center for Research Resources of the National Institutes of Health.

PY - 2013/10

Y1 - 2013/10

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.

AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84884914010&partnerID=8YFLogxK

U2 - 10.1093/molehr/gat036

DO - 10.1093/molehr/gat036

M3 - Article

C2 - 23689979

AN - SCOPUS:84884914010

SN - 1360-9947

VL - 19

SP - 687

EP - 696

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

IS - 10

M1 - gat036

ER -

Localization of a major susceptibility locus influencing preterm birth

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