Study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth

INTRODUCTION: A short cervix (cervical length <25 mm) in the midtrimester (18–24 weeks) of pregnancy is a powerful predictor of spontaneous preterm delivery. Although the biological mechanisms of cervical change during pregnancy have been the subject of extensive investigation, little is known ab...

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Autores principales: Wolf, Hope M, Romero, Roberto, Strauss, Jerome F, Hassan, Sonia S, Latendresse, Shawn J, Webb, Bradley T, Tarca, Adi L, Gomez-Lopez, Nardhy, Hsu, Chaur-Dong, York, Timothy P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932269/
https://www.ncbi.nlm.nih.gov/pubmed/35301205
http://dx.doi.org/10.1136/bmjopen-2021-053631
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author Wolf, Hope M
Romero, Roberto
Strauss, Jerome F
Hassan, Sonia S
Latendresse, Shawn J
Webb, Bradley T
Tarca, Adi L
Gomez-Lopez, Nardhy
Hsu, Chaur-Dong
York, Timothy P
author_facet Wolf, Hope M
Romero, Roberto
Strauss, Jerome F
Hassan, Sonia S
Latendresse, Shawn J
Webb, Bradley T
Tarca, Adi L
Gomez-Lopez, Nardhy
Hsu, Chaur-Dong
York, Timothy P
author_sort Wolf, Hope M
collection PubMed
description INTRODUCTION: A short cervix (cervical length <25 mm) in the midtrimester (18–24 weeks) of pregnancy is a powerful predictor of spontaneous preterm delivery. Although the biological mechanisms of cervical change during pregnancy have been the subject of extensive investigation, little is known about whether genes influence the length of the cervix, or the extent to which genetic factors contribute to premature cervical shortening. Defining the genetic architecture of cervical length is foundational to understanding the aetiology of a short cervix and its contribution to an increased risk of spontaneous preterm delivery. METHODS/ANALYSIS: The proposed study is designed to characterise the genetic architecture of cervical length and its genetic relationship to gestational age at delivery in a large cohort of Black/African American women, who are at an increased risk of developing a short cervix and delivering preterm. Repeated measurements of cervical length will be modelled as a longitudinal growth curve, with parameters estimating the initial length of the cervix at the beginning of pregnancy, and its rate of change over time. Genome-wide complex trait analysis methods will be used to estimate the heritability of cervical length growth parameters and their bivariate genetic correlation with gestational age at delivery. Polygenic risk profiling will assess maternal genetic risk for developing a short cervix and subsequently delivering preterm and evaluate the role of cervical length in mediating the relationship between maternal genetic variation and gestational age at delivery. ETHICS/DISSEMINATION: The proposed analyses will be conducted using deidentified data from participants in an IRB-approved study of longitudinal cervical length who provided blood samples and written informed consent for their use in future genetic research. These analyses are preregistered with the Center for Open Science using the AsPredicted format and the results and genomic summary statistics will be published in a peer-reviewed journal.
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spelling pubmed-89322692022-04-01 Study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth Wolf, Hope M Romero, Roberto Strauss, Jerome F Hassan, Sonia S Latendresse, Shawn J Webb, Bradley T Tarca, Adi L Gomez-Lopez, Nardhy Hsu, Chaur-Dong York, Timothy P BMJ Open Obstetrics and Gynaecology INTRODUCTION: A short cervix (cervical length <25 mm) in the midtrimester (18–24 weeks) of pregnancy is a powerful predictor of spontaneous preterm delivery. Although the biological mechanisms of cervical change during pregnancy have been the subject of extensive investigation, little is known about whether genes influence the length of the cervix, or the extent to which genetic factors contribute to premature cervical shortening. Defining the genetic architecture of cervical length is foundational to understanding the aetiology of a short cervix and its contribution to an increased risk of spontaneous preterm delivery. METHODS/ANALYSIS: The proposed study is designed to characterise the genetic architecture of cervical length and its genetic relationship to gestational age at delivery in a large cohort of Black/African American women, who are at an increased risk of developing a short cervix and delivering preterm. Repeated measurements of cervical length will be modelled as a longitudinal growth curve, with parameters estimating the initial length of the cervix at the beginning of pregnancy, and its rate of change over time. Genome-wide complex trait analysis methods will be used to estimate the heritability of cervical length growth parameters and their bivariate genetic correlation with gestational age at delivery. Polygenic risk profiling will assess maternal genetic risk for developing a short cervix and subsequently delivering preterm and evaluate the role of cervical length in mediating the relationship between maternal genetic variation and gestational age at delivery. ETHICS/DISSEMINATION: The proposed analyses will be conducted using deidentified data from participants in an IRB-approved study of longitudinal cervical length who provided blood samples and written informed consent for their use in future genetic research. These analyses are preregistered with the Center for Open Science using the AsPredicted format and the results and genomic summary statistics will be published in a peer-reviewed journal. BMJ Publishing Group 2022-03-17 /pmc/articles/PMC8932269/ /pubmed/35301205 http://dx.doi.org/10.1136/bmjopen-2021-053631 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Obstetrics and Gynaecology
Wolf, Hope M
Romero, Roberto
Strauss, Jerome F
Hassan, Sonia S
Latendresse, Shawn J
Webb, Bradley T
Tarca, Adi L
Gomez-Lopez, Nardhy
Hsu, Chaur-Dong
York, Timothy P
Study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth
title Study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth
title_full Study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth
title_fullStr Study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth
title_full_unstemmed Study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth
title_short Study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth
title_sort study protocol to quantify the genetic architecture of sonographic cervical length and its relationship to spontaneous preterm birth
topic Obstetrics and Gynaecology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932269/
https://www.ncbi.nlm.nih.gov/pubmed/35301205
http://dx.doi.org/10.1136/bmjopen-2021-053631
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