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Protocol for a longitudinal twin birth cohort study to unravel the complex interplay between early-life environmental and genetic risk factors in health and disease: the Chongqing Longitudinal Twin Study (LoTiS)
  1. Chao Tong1,2,
  2. Li Wen1,2,
  3. Yinyin Xia2,3,
  4. Pamela Leong4,5,6,
  5. Lan Wang7,
  6. Xin Fan8,
  7. Ting-li Han9,
  8. Jeffrey M Craig5,
  9. Philip Baker5,10,
  10. Richard Saffery4,6,
  11. Hongbo Qi1,2
  1. 1 Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  2. 2 Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
  3. 3 Department of Occupational and Environmental Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing, China
  4. 4 Cancer, Disease and Developmental Epigenetics, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia
  5. 5 Early Life Epigenetics, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia
  6. 6 Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  7. 7 Department of Obstetrics, Chongqing Health Centre for Women and Children, Chongqing, China
  8. 8 Department of Pediatrics, Chongqing Health Centre for Women and Children, Chongqing, China
  9. 9 Liggins Institute, University of Auckland, Auckland, New Zealand
  10. 10 College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK
  1. Correspondence to Professor Hongbo Qi; qihongbo{at}sina.com

Abstract

Introduction Non-communicable diseases (NCD) now represent the major burden of adverse health in most countries. It is clear that much of the risk of such conditions begins very early in life, potentially in utero. Given their complex aetiology, an understanding of the origins of NCD requires an in-depth analysis of the interplay between genetic variation and environment, preferably over time. For decades, twin studies have played a key role in understanding such traits. Their strength lies in the ability to disentangle genetic and environmental factors that contribute to a phenotype. This is done by comparing genetically identical monozygotic (MZ) with dizygotic twins, who share on average 50% of genetic variation, or by comparing MZ twins within a pair. This study aims to determine the relative contributions of genes and environment to early-onset intermediate phenotypes related to later adult onset disease (such as growth and neurodevelopment) and to identify specific biomarkers and time points for emergence of phenotypes from infancy, largely independent of underlying genetic factors.

Methods/design The Chongqing Longitudinal Twin Study (LoTiS) will recruit 300 women pregnant with twins, enriched for MZ pregnancies, with follow-up to 3 years of age. Data collection will be undertaken at key time points in gestation (×3), at delivery and postnatally (×9). Maternal and infant biospecimens including blood, urine, hair, nails and buccal swabs along with measures such as fetal scans and body measurements will be collected. Additional information from questionnaires and medical records includes pregnancy, diet, sociodemographics, maternal stress, and infant growth and neurodevelopment.

Ethics and dissemination This study has been approved by the Ethics Committee of Chongqing Medical University (record no: 201530) and has been registered with the Chinese Clinical Trial Registry (registry no: ChiCTR-OOC-16008203). Results of the recruitment and all subsequent analyses will be submitted for publication in peer-reviewed journals.

Trial registration number ChiCTR-OOC-16008203; Results.

  • twins
  • birth cohort
  • longitudinal
  • epigenetics
  • monozygotic
  • dizygotic

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 and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • C.T, LW, RS and HQ contributed equally.

  • Contributors PB, CT, HQ and RS conceptualised, developed and secured funding for the study. CT, LW, YX, LW, XF, TH and JMC produced the standard operating procedures and tested their utility prior to commencement of recruitment. This included quality control measures and protocol refinements. CT, LW, PL and RS wrote the manuscript that was refined and finalised with the help of all authors. Each read and approved the final version.

  • Funding This work was supported by grants from the National Natural Sciences Foundation of China (81520108013 to HQ; 81671488 to CT), Ministry of Science and Technology (2016YFC1000407 to HQ), Chongqing Municipal Education Commission (CXTDX201601014 to HQ, KJ1500223 to CT). RS is funded by the National Health and Medical Research Council (Australia; GNT1045161) and the Victorian Government operational infrastructure scheme.

  • Competing interests None declared.

  • Patient consent Parental/guardian consent obtained.

  • Ethics approval This study has been approved by the Ethics Committee of Chongqing Medical University (record no: 201530) and has been registered with the Chinese Clinical Trial Registry (registry no ChiCTR-OOC-16008203).

  • Provenance and peer review Not commissioned; externally peer reviewed.