Introduction

Despite a decrease in the mortality rates of sudden infant death syndrome (SIDS) over the past decades, SIDS is still one of the leading causes of post-neonatal and infant death. In the United States, 8% of all infant deaths are attributed to SIDS, only behind congenital malformations and chromosomal abnormalities (21%) and disorders relating to prematurity and low birth weight (17%) (1). While efforts have been made to reduce the role of environmental factors, such as sleep environment and smoking, this persistent mortality highlights the importance of intrinsic factors involved in SIDS, including genetic changes that predispose infants to, or are directly responsible for, SIDS (2, 3). In addition, the incidence of SIDS in families where one infant has died from SIDS is increased by over fivefold, providing further evidence of a role for genetic factors (4, 5).

A role for genetic factors in SIDS is consistent with the Triple Risk Model of SIDS, with genetic factors contributing to the “vulnerable infant”. The Triple Risk Model hypothesizes that three elements are present for SIDS to occur (6):

According to the Triple Risk Model, although most babies encounter and survive environmental stressors, a vulnerable infant who becomes challenged during a critical period may not be able to overcome the stressor, leading to SIDS. Thus, SIDS can be seen as representing a severe, lethal phenotype with genetic causes that contribute to the vulnerable infant. Genomic approaches to SIDS attempt to understand genetic mechanisms causing or contributing to this infant vulnerability.