Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population.
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 m...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0269671 |
| _version_ | 1811208563175981056 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sushil Bhandari |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T04:23:28Z |
| format | Article |
| id | doaj.art-9a81fd1b14cb4291b5ae33fc2db91ad6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T04:23:28Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9a81fd1b14cb4291b5ae33fc2db91ad62022-12-22T03:48:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01179e026967110.1371/journal.pone.0269671Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population.Sushil BhandariPadma DolmaMitali MukerjiBhavana PrasherHugh MontgomeryDalvir KularVandana JainVatsla DadhwalDavid J WilliamsAniket BhattacharyaaEdmund GilbertGianpiero L CavalleriSara L HillmanPathological 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.https://doi.org/10.1371/journal.pone.0269671 |
| spellingShingle | 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 Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population. PLoS ONE |
| title | Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population. |
| title_full | Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population. |
| title_fullStr | Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population. |
| title_full_unstemmed | Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population. |
| title_short | Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population. |
| title_sort | population history and genome wide association studies of birth weight in a native high altitude ladakhi population |
| url | https://doi.org/10.1371/journal.pone.0269671 |
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