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Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population.pdf (1.48 MB)

Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population

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posted on 2023-11-13, 16:52 authored by Sushil Bhandari, Padma Dolma, Mitali Mukerji, Bhavana Prasher, Hugh Montgomery, Dalvir Kular, Vandana Jain, Vatsla Dadhwal, David J Williams, Aniket Bhattacharyaa, Edmund GilbertEdmund Gilbert, Gianpiero CavalleriGianpiero Cavalleri, Sara L. Hillman
Pathological low birth weight due to fetal growth restriction (FGR) is an important predictor of adverse obstetric and neonatal outcomes. It is more common amongst native lowlanders when gestating in the hypoxic environment of high altitude, whilst populations who have resided at high altitude for many generations are relatively protected. Genetic study of pregnant populations at high altitude permits exploration of the role of hypoxia in FGR pathogenesis, and perhaps of FGR pathogenesis more broadly. We studied the umbilical cord blood DNA of 316 neonates born to pregnant women managed at the Sonam Norboo Memorial Hospital, Ladakh (altitude 3540m) between February 2017 and January 2019. Principal component, admixture and genome wide association studies (GWAS) were applied to dense single nucleotide polymorphism (SNP) genetic data, to explore ancestry and genetic predictors of low birth weight. Our findings support Tibetan ancestry in the Ladakhi population, with subsequent admixture with neighboring Indo-Aryan populations. Fetal growth protection was evident in Ladakhi neonates. Although no variants achieved genome wide significance, we observed nominal association of seven variants across genes (ZBTB38, ZFP36L2, HMGA2, CDKAL1, PLCG1) previously associated with birthweight.

Funding

Wellcome Trust SEED trust award (WT 109862/Z/15/Z)

UCL Global Health Challenges award

Eden Travelling Fellowship from the Royal College of Obstetricians and Gynaecologists

UK National Institute for Health Research’s Comprehensive Biomedical Research Centre

Government of Ireland Postdoctoral Fellowship from the Irish Research Council (GOIPD/2018/408)

History

Comments

The original article is available at https://journals.plos.org/ Pre-print is available on bioRxiv. https://doi.org/10.1101/2022.05.26.493635 and RCSI repository https://hdl.handle.net/10779/rcsi.25205570.v1

Published Citation

Bhandari S. et al. Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population. PLoS One. 2022;17(9):e0269671.

Publication Date

20 September 2022

PubMed ID

36126061

Department/Unit

  • School of Pharmacy and Biomolecular Sciences
  • FutureNeuro Centre

Research Area

  • Neurological and Psychiatric Disorders

Publisher

Public Library of Science (PLoS)

Version

  • Published Version (Version of Record)