Genetic Associations in Preterm Birth: A Primer of Marker Selection, Study Design, and Data Analysis

Ramkumar Menon, Stephen J. Fortunato, Poul Thorsen, Scott Williams

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Spontaneous preterm birth (PTB; delivery before 37 weeks gestation) is a primary risk factor for infant morbidity and mortality. The etiology is unclear, but there is evidence that there is a genetic predisposition to PTB. Armed with the suggestion of genetic risk factors and the failure to identify useful biomarkers, investigators are starting to actively pursue the role of genetic predisposition in PTB. Several studies have been done to date assessing the role of single gene variants. However, positive findings have failed to replicate. We argue that heterogeneity in study designs, definition of phenotype, single-nucleotide polymorphism (SNP) selection, population selection, and sample size makes data interpretation difficult in complex phenotypes such as PTB. In this review, we introduce general concepts of study designs in genetic epidemiology, selection of candidate genes and markers for analysis, and analytical methodologies. We also introduce how the concept of gene-gene interactions (biologic epistasis) and gene-environment interactions may affect the predisposition to PTB.

Original languageEnglish (US)
Pages (from-to)531-541
Number of pages11
JournalJournal of the Society for Gynecologic Investigation
Volume13
Issue number8
DOIs
StatePublished - Dec 2006
Externally publishedYes

Fingerprint

Premature Birth
Genetic Predisposition to Disease
Genes
Phenotype
Gene-Environment Interaction
Molecular Epidemiology
Genetic Association Studies
Infant Mortality
Population Density
Sample Size
Single Nucleotide Polymorphism
Biomarkers
Research Personnel
Morbidity
Pregnancy

Keywords

  • Genetic association
  • MDR
  • multilocus analysis
  • prematurity
  • single-nucleotide polymorphisms

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Genetic Associations in Preterm Birth : A Primer of Marker Selection, Study Design, and Data Analysis. / Menon, Ramkumar; Fortunato, Stephen J.; Thorsen, Poul; Williams, Scott.

In: Journal of the Society for Gynecologic Investigation, Vol. 13, No. 8, 12.2006, p. 531-541.

Research output: Contribution to journalArticle

@article{dfb21b06908e40ee920ee5410cccf7c9,
title = "Genetic Associations in Preterm Birth: A Primer of Marker Selection, Study Design, and Data Analysis",
abstract = "Spontaneous preterm birth (PTB; delivery before 37 weeks gestation) is a primary risk factor for infant morbidity and mortality. The etiology is unclear, but there is evidence that there is a genetic predisposition to PTB. Armed with the suggestion of genetic risk factors and the failure to identify useful biomarkers, investigators are starting to actively pursue the role of genetic predisposition in PTB. Several studies have been done to date assessing the role of single gene variants. However, positive findings have failed to replicate. We argue that heterogeneity in study designs, definition of phenotype, single-nucleotide polymorphism (SNP) selection, population selection, and sample size makes data interpretation difficult in complex phenotypes such as PTB. In this review, we introduce general concepts of study designs in genetic epidemiology, selection of candidate genes and markers for analysis, and analytical methodologies. We also introduce how the concept of gene-gene interactions (biologic epistasis) and gene-environment interactions may affect the predisposition to PTB.",
keywords = "Genetic association, MDR, multilocus analysis, prematurity, single-nucleotide polymorphisms",
author = "Ramkumar Menon and Fortunato, {Stephen J.} and Poul Thorsen and Scott Williams",
year = "2006",
month = "12",
doi = "10.1016/j.jsgi.2006.09.006",
language = "English (US)",
volume = "13",
pages = "531--541",
journal = "Reproductive Sciences",
issn = "1933-7191",
publisher = "SAGE Publications Inc.",
number = "8",

}

TY - JOUR

T1 - Genetic Associations in Preterm Birth

T2 - A Primer of Marker Selection, Study Design, and Data Analysis

AU - Menon, Ramkumar

AU - Fortunato, Stephen J.

AU - Thorsen, Poul

AU - Williams, Scott

PY - 2006/12

Y1 - 2006/12

N2 - Spontaneous preterm birth (PTB; delivery before 37 weeks gestation) is a primary risk factor for infant morbidity and mortality. The etiology is unclear, but there is evidence that there is a genetic predisposition to PTB. Armed with the suggestion of genetic risk factors and the failure to identify useful biomarkers, investigators are starting to actively pursue the role of genetic predisposition in PTB. Several studies have been done to date assessing the role of single gene variants. However, positive findings have failed to replicate. We argue that heterogeneity in study designs, definition of phenotype, single-nucleotide polymorphism (SNP) selection, population selection, and sample size makes data interpretation difficult in complex phenotypes such as PTB. In this review, we introduce general concepts of study designs in genetic epidemiology, selection of candidate genes and markers for analysis, and analytical methodologies. We also introduce how the concept of gene-gene interactions (biologic epistasis) and gene-environment interactions may affect the predisposition to PTB.

AB - Spontaneous preterm birth (PTB; delivery before 37 weeks gestation) is a primary risk factor for infant morbidity and mortality. The etiology is unclear, but there is evidence that there is a genetic predisposition to PTB. Armed with the suggestion of genetic risk factors and the failure to identify useful biomarkers, investigators are starting to actively pursue the role of genetic predisposition in PTB. Several studies have been done to date assessing the role of single gene variants. However, positive findings have failed to replicate. We argue that heterogeneity in study designs, definition of phenotype, single-nucleotide polymorphism (SNP) selection, population selection, and sample size makes data interpretation difficult in complex phenotypes such as PTB. In this review, we introduce general concepts of study designs in genetic epidemiology, selection of candidate genes and markers for analysis, and analytical methodologies. We also introduce how the concept of gene-gene interactions (biologic epistasis) and gene-environment interactions may affect the predisposition to PTB.

KW - Genetic association

KW - MDR

KW - multilocus analysis

KW - prematurity

KW - single-nucleotide polymorphisms

UR - http://www.scopus.com/inward/record.url?scp=33845451012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845451012&partnerID=8YFLogxK

U2 - 10.1016/j.jsgi.2006.09.006

DO - 10.1016/j.jsgi.2006.09.006

M3 - Article

C2 - 17088082

AN - SCOPUS:33845451012

VL - 13

SP - 531

EP - 541

JO - Reproductive Sciences

JF - Reproductive Sciences

SN - 1933-7191

IS - 8

ER -