Evidence for ethnicity and location as regulators of the newborn blood metabolome: a monozygous twin study

Huimin Jiang; Ting-Li Han; Jing Yang; Yang Yang; Fengdi Wang; Yuelu Chen; Nana Huang; Toby Mansell; Jeffrey M Craig; Katrina J Scurrah; Boris Novakovic; Philip N Baker; Hua Zhang; Yuan Wei; Lianlian Wang; Richard Saffery

doi:10.3389/fnut.2023.1259777

Evidence for ethnicity and location as regulators of the newborn blood metabolome: a monozygous twin study

Front Nutr. 2024 Jan 4:10:1259777. doi: 10.3389/fnut.2023.1259777. eCollection 2023.

Authors

Huimin Jiang^#¹, Ting-Li Han^#², Jing Yang^#³, Yang Yang^{4

5

6}, Fengdi Wang¹, Yuelu Chen¹, Nana Huang³, Toby Mansell⁷, Jeffrey M Craig^{7

8}, Katrina J Scurrah⁹, Boris Novakovic⁷, Philip N Baker¹⁰, Hua Zhang^{4

5}, Yuan Wei³, Lianlian Wang¹, Richard Saffery⁷

Affiliations

¹ Department of Reproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
³ Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
⁴ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁵ Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China.
⁶ Mass Spectrometry Centre of Maternal-Fetal Medicine, Life Science Institution, Chongqing Medical University, Chongqing, China.
⁷ Murdoch Children's Research Institute, and Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
⁸ The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Melbourne, VIC, Australia.
⁹ Twins Research Australia and Centre for Mental Health, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
¹⁰ College of Life Sciences, University of Leicester, Leicester, United Kingdom.

^# Contributed equally.

Abstract

Introduction: Monochorionic, diamniotic (MCDA) monozygotic twins share nearly all genetic variation and a common placenta in utero. Despite this, MCDA twins are often discordant for a range of common phenotypes, including early growth and birth weight. As such, MCDA twins represent a unique model to explore variation in early growth attributable primarily to in utero environmental factors.

Methods: MCDA twins with a range of within-pair birth weight discordance were sampled from the peri/postnatal epigenetic twin study (PETS, Melbourne; n = 26 pairs), Beijing twin study (BTS, Beijing; n = 25), and the Chongqing longitudinal twin study (LoTiS, Chongqing; n = 22). All PETS participants were of European-Australian ancestry, while all Chinese participants had Han ancestry. The average of the birth weight difference between the larger and smaller co-twins for all twin pairs was determined and metabolomic profiles of amino acids, TCA cycle intermediates, fatty acids, organic acids, and their derivatives generated from cord blood plasma by gas chromatograph mass spectrometry. Within and between co-twin pair analyses were performed to identify metabolites specifically associated with discordance in birth weight. Multivariable regression and pathway enrichment analyses between different regions were performed to evaluate the geographical effects on the metabolism of MCDA twin pairs.

Results: PETS twins showed a markedly different metabolic profile at birth compared to the two Chinese samples. Within-pair analysis revealed an association of glutathione, creatinine, and levulinic acid with birth weight discordance. Caffeine, phenylalanine, and several saturated fatty acid levels were uniquely elevated in PETS twins and were associated with maternal BMI and average within pair birth weight, in addition to birth weight discordance. LoTiS twins had higher levels of glutathione, tyrosine, and gamma-linolenic acid relative to PETS and BTS twins, potentially associated with eating habits.

Conclusion: This study highlights the potential role of underlying genetic variation (shared by MZ twins), in utero (non-shared by MZ twins) and location-specific (shared by MZ twins) environmental factors, in regulating the cord blood metabolome of uncomplicated MCDA twins. Future research is needed to unravel these complex relationships that may play a key role in phenotypic metabolic alterations of twins independent of genetic diversity.

Keywords: metabolomics; monochorionic diamniotic (MCDA) twins; shared and non-shared environmental factors; umbilical cord blood plasma; uncomplicated MCDA twins.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from Joint Program of the Chongqing Science and Technology Bureau and the Chongqing Health Commission (2021MSXM215), Chongqing Science and Technology Commission (CSTB2023NSCQ-MSX0535), Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0041), National Natural Sciences Foundation of China (81520108013), the 111 program of the Ministry of Education P.R.C and the State Administration of Foreign Experts Affairs P.R.C., the Natural Science Foundation of Beijing (7212133), the Emerging Engineering Interdisciplinary-Young Scholars Project, Peking University, the Fundamental Research Funds for the Cornell University (PKU2023XGK015), and Key Laboratory of Birth Defects and Reproductive Health of National Health and Family Planning Commission P.R.C.