TY  - BOOK
AU  - Reddy, Uma M
TI  - Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms
SN  - 0002-9378
PY  - 2015///
KW  - *Phenotype
KW  - *Premature Birth/et [Etiology]
KW  - Adult
KW  - Case-Control Studies
KW  - Cluster Analysis
KW  - Female
KW  - Genetic Markers
KW  - Genotype
KW  - Humans
KW  - Insulin/ge [Genetics]
KW  - Logistic Models
KW  - Polymorphism, Single Nucleotide
KW  - Pregnancy
KW  - Premature Birth/ge [Genetics]
KW  - Prospective Studies
KW  - Risk Factors
KW  - MedStar Washington Hospital Center
KW  - Obstetrics and Gynecology, Maternal-Fetal Medicine
KW  - Journal Article
KW  - Multicenter Study
KW  - Research Support, N.I.H., Extramural
N1  - Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
N2  - 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.Copyright � 2015 Elsevier Inc. All rights reserved; 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; 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 chi(2) 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; 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
UR  - http://dx.doi.org/10.1016/j.ajog.2015.06.011
ER  -