# **RESEARCH ABSTRACT** --- #### **Title:** Methods to Quantify the Genetic Architecture of Cervical Length. <br> #### **Introduction:** A short cervix (cervical length < 25 mm) in the midtrimester (18 to 24 weeks) of pregnancy is a powerful predictor of preterm birth. Although the biological mechanisms of cervical change over the course of pregnancy have been the subject of extensive investigation, very little is known about the genetic architecture of cervical length, or the extent to which genetic factors contribute to premature cervical shortening. We have developed longitudinal models of cervical length change across pregnancy that, when combined with genomic data, can be used to estimate the heritability of cervical length and its genetic covariance with gestational age at birth. <br> #### **Methods:** Latent growth curves were established to model cervical change for a large cohort of women with longitudinal assessments of cervical length across pregnancy. Cervical length was measured in millimeters using transvaginal ultrasound. Baseline cervical length was measured between 18 and 24 weeks of gestation, and 1 to 15 additional measurements were collected for each subject during follow-up. Demographic characteristics, including relevant medical history and birth outcome data, were collected for each subject. Gestational age at birth was measured from the first day of the woman’s last menstrual period and confirmed by obstetrical ultrasound. <br> #### **Results:** The latent growth curve describes cervical change as a function of time using two classes of parameters: intercept terms, which account for inter-individual variability in the baseline value of cervical length, and polynomial terms, which capture individual departures in the rate of change from the population mean. We describe how the parameters of the model can be combined with genomic and birth outcome data to make predictions about the genetic architecture of cervical change across pregnancy and its genetic relationship to spontaneous preterm birth. <br> #### **Conclusions:** An estimate for the genetic contribution to cervical length and its role in mediating the timing of birth is essential to understanding the pathophysiology of spontaneous preterm birth. The methods we have developed will allow us to estimate the heritability of cervical length and its bivariate genetic correlation with gestational age at birth. Extensions of this model can be used to develop a polygenic risk score which could be applied in clinical practice to rapidly assess a patient’s genetic risk for developing a short cervix and delivering preterm. <br> #### **Authors:** **Hope M Wolf†** (1), Roberto Romero (2), Jerome F Strauss, III (1), Sonia S Hassan (3), Shawn J Latendresse (4), Bradley T Webb (1), Aaron R Wolen (5), Adi L Tarca (3), Timothy P York (1). 1) Virginia Commonwealth University School of Medicine, Richmond, VA, United States. 2) Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Rockville, MD, United States. 3) Wayne State University School of Medicine, Detroit, MI, United States. 4) Baylor University, Waco, TX, United States; 5) The University of Tennessee Health Science Center, Memphis, TN, United States.