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

Author

Listed:
  • Sushil Bhandari
  • Padma Dolma
  • Mitali Mukerji
  • Bhavana Prasher
  • Hugh Montgomery
  • Dalvir Kular
  • Vandana Jain
  • Vatsla Dadhwal
  • David J Williams
  • Aniket Bhattacharyaa
  • Edmund Gilbert
  • Gianpiero L Cavalleri
  • Sara L Hillman

Abstract

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.

Suggested Citation

  • Sushil Bhandari & Padma Dolma & Mitali Mukerji & Bhavana Prasher & Hugh Montgomery & Dalvir Kular & Vandana Jain & Vatsla Dadhwal & David J Williams & Aniket Bhattacharyaa & Edmund Gilbert & Gianpiero, 2022. "Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population," PLOS ONE, Public Library of Science, vol. 17(9), pages 1-13, September.
    • Handle: RePEc:plo:pone00:0269671
    DOI: 10.1371/journal.pone.0269671
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    1. Momoko Horikoshi & Robin N. Beaumont & Felix R. Day & Nicole M. Warrington & Marjolein N. Kooijman & Juan Fernandez-Tajes & Bjarke Feenstra & Natalie R. van Zuydam & Kyle J. Gaulton & Niels Grarup & J, 2016. "Genome-wide associations for birth weight and correlations with adult disease," Nature, Nature, vol. 538(7624), pages 248-252, October.
    2. Daniel John Lawson & Garrett Hellenthal & Simon Myers & Daniel Falush, 2012. "Inference of Population Structure using Dense Haplotype Data," PLOS Genetics, Public Library of Science, vol. 8(1), pages 1-16, January.
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