Maternal Genetic Variation and Risk of Adverse Pregnancy Outcomes

Preterm birth, small-for-gestational age (SGA) and pregnancy induced hypertension (PIH) are major pregnancy complications that impact the health of the mother and the child, often resulting in admission to the neonatal intensive care unit following delivery. We are conducting a highly efficient, intensive pathway-based analysis of genetic variation and preterm delivery, SGA, and PIH that addresses the following specific aims: (1) To investigate the relationship between polymorphisms in the cell-cycle and apoptosis pathways with risk of preterm delivery, SGA, Term SGA and pregnancy induced hypertension (PIH); (2) To investigate the relationship between polymorphisms in the angiogenesis pathway with risk of SGA and PIH; (3) To investigate the relationship between polymorphisms in the inflammation pathway with risk of preterm delivery, total and term SGA, and PIH. To address these aims we are drawing on a well-characterized prospective cohort study of preterm delivery, the Pregnancy, Infection and Nutrition study (PIN), which enrolled over five thousand women over the course of approximately 10 years. In a nested case-control subset of preterm, SGA, and PIH cases and a random group of controls, DNA has already been extracted and is available for genetic analyses. We will analyze these DNA specimens using a haplotype-based approach for approximately 93 genes of interest on the Illumina 1536 chip. The priority pathways we have identified bear relevance to the period of placentation, which may be the period of development at which these outcomes are etiologically linked. With a small additional investment, this cohort could provide the most comprehensive evidence to date linking variants in these pathways of interest with these adverse birth outcomes, while allowing for further investigations of gene-gene, and gene-environment interactions using a host of already collected infection, nutrition, and life-style information.

Principal Investigators: Andrew F. Olshan, Engel, Stephanie (Overall PI, Mt. Sinai School of Medicine)

CPC Fellow Investigators: Amy H. Herring

Funding Source: NIH

Grant Number: R21HD060207

Funding Period: 05/15/09-04/30/11