Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms Presented, in part, in poster format at the 35th annual meeting of the Society for Maternal-Fetal Medicine San Diego, CA, Feb. 2-7, 2015.

M. Sean Esplin, Tracy A. Manuck, Michael W. Varner, Bryce Christensen, Joseph Biggio, Radek Bukowski, Samuel Parry, Heping Zhang, Hao Huang, William Andrews, George Saade, Yoel Sadovsky, Uma M. Reddy, John Ilekis

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. Study Design We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. Results One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P =.0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB.

Original languageEnglish (US)
Pages (from-to)429e1-429e9
JournalAmerican Journal of Obstetrics and Gynecology
Volume213
Issue number3
DOIs
StatePublished - Sep 1 2015

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Posters
Premature Birth
Cluster Analysis
Phenotype
Hemorrhage
Infection
Mothers
Insulin
Genes
Genetic Association Studies
Multicenter Studies
Case-Control Studies
Comorbidity
Rupture
Software
Research Personnel
Pregnancy
Membranes

Keywords

  • cluster analysis
  • gene-based analysis
  • phenotype
  • spontaneous preterm birth

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms Presented, in part, in poster format at the 35th annual meeting of the Society for Maternal-Fetal Medicine San Diego, CA, Feb. 2-7, 2015. / Esplin, M. Sean; Manuck, Tracy A.; Varner, Michael W.; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John.

In: American Journal of Obstetrics and Gynecology, Vol. 213, No. 3, 01.09.2015, p. 429e1-429e9.

Research output: Contribution to journalArticle

Esplin, M. Sean ; Manuck, Tracy A. ; Varner, Michael W. ; Christensen, Bryce ; Biggio, Joseph ; Bukowski, Radek ; Parry, Samuel ; Zhang, Heping ; Huang, Hao ; Andrews, William ; Saade, George ; Sadovsky, Yoel ; Reddy, Uma M. ; Ilekis, John. / Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms Presented, in part, in poster format at the 35th annual meeting of the Society for Maternal-Fetal Medicine San Diego, CA, Feb. 2-7, 2015. In: American Journal of Obstetrics and Gynecology. 2015 ; Vol. 213, No. 3. pp. 429e1-429e9.
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abstract = "Objective We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. Study Design We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. Results One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P =.0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB.",
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AU - Esplin, M. Sean

AU - Manuck, Tracy A.

AU - Varner, Michael W.

AU - Christensen, Bryce

AU - Biggio, Joseph

AU - Bukowski, Radek

AU - Parry, Samuel

AU - Zhang, Heping

AU - Huang, Hao

AU - Andrews, William

AU - Saade, George

AU - Sadovsky, Yoel

AU - Reddy, Uma M.

AU - Ilekis, John

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N2 - Objective We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. Study Design We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. Results One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P =.0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB.

AB - Objective We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. Study Design We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. Results One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P =.0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB.

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