Genetic contributions to risk of adverse pregnancy outcomes.

Abstract

Adverse pregnancy outcomes (APOs), including hypertensive disorders of pregnancy (HDP), low birthweight (LBW), and preterm birth (PTB), along with peripartum cardiomyopathy (PPCM) are associated with short- and long-term maternal and fetal cardiovascular risks. This review focuses on the genetic contributions to the risk of APOs and PPCM. The expansion of genome-wide association studies (GWAS) has led to better understanding of the biologic mechanisms underpinning APO, PPCM, and the predisposition to cardiovascular disease across the life course. Genetic loci known to be involved with the risk of hypertension (FTO, ZNF831) have been associated with the development of overall HDP and preeclampsia. Additionally, four loci significantly associated with type 2 diabetes have been associated with GDM (CDKAL1, MTNR1B, TCF7L2, CDK2NA-CDKN2B). Variants in loci known to affect genes coding for proteins involved in immune cell function and placental health (EBF1, EEFSEC, AGTR2, 2q13) have been implicated in the development of PTB and future cardiovascular risks for both the mother and the offspring. Genetic similarities in rare variants between PPCM and dilated cardiomyopathy have been described suggesting shared pathophysiologic origins as well as predisposition for future risk of heart failure, highlighting the need for the development PPCM genetic counseling guidelines. Genetics may inform mechanisms, risk, and counseling for individuals after an APO or PPCM. Through recent advances in genetic techniques and analytic approaches, new insights into the underlying biologic mechanisms and genetic variants leading to these risks have been discovered.