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Babies of South Asian and European ancestry show similar associations with genetic risk score for birth weight despite the smaller size of South Asian newborns

Babies of South Asian and European ancestry show similar associations with genetic risk score for birth weight despite the smaller size of South Asian newborns
Babies of South Asian and European ancestry show similar associations with genetic risk score for birth weight despite the smaller size of South Asian newborns

Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from these cohorts were compared with South Asians in UK Biobank and the Exeter Family Study of Childhood Health, a European ancestry cohort. Birth weight increased by 50.7 g and 33.6 g per SD of fGS (P = 9.1 × 10-11) and mGS (P = 0.003), respectively, in South Asians. A relatively weaker mGS effect compared with Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birth weight was strongly associated with body size in both childhood and adolescence (P = 3 × 10-5 to 1.9 × 10-51); however, fGS was associated with body size in childhood only (P < 0.01) and with head circumference, fasting glucose, and triglycerides in adults (P < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birth weight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status, etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism that partly explains associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians.

0012-1797
821-836
Nongmaithem, Suraj N.
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Beaumont, Robin N.
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Dedaniya, Akshay
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Wood, Andrew R.
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Ogunkolade, Babatunji-William
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Hassan, Zahid
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Krishnaveni, Ghattu V.
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Kumaran, Kalyanaraman
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Potdar, Ramesh D.
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Sahariah, Sirazul A.
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Krishna, Murali
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Di Gravio, Chiara
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Mali, Inder D
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Sankareswaran, Alagu
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Hussain, Akhtar
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Bhowmik, Biswajit W
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Khan, Abdul Kalam A.
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Knight, Bridget A.
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Frayling, Timothy M.
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Finer, Sarah
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Fall, Caroline
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Yajnik, Chittaranjan S.
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Freathy, Rachel M.
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Hitman, Graham A.
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Chandak, Giriraj R.
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Nongmaithem, Suraj N.
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Beaumont, Robin N.
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Dedaniya, Akshay
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Wood, Andrew R.
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Hassan, Zahid
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Kumaran, Kalyanaraman
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Potdar, Ramesh D.
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Sahariah, Sirazul A.
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Krishna, Murali
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Di Gravio, Chiara
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Mali, Inder D
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Sankareswaran, Alagu
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Hussain, Akhtar
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Bhowmik, Biswajit W
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Khan, Abdul Kalam A.
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Knight, Bridget A.
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Frayling, Timothy M.
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Finer, Sarah
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Fall, Caroline
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Yajnik, Chittaranjan S.
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Freathy, Rachel M.
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Hitman, Graham A.
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Chandak, Giriraj R.
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Nongmaithem, Suraj N., Beaumont, Robin N., Dedaniya, Akshay, Wood, Andrew R., Ogunkolade, Babatunji-William, Hassan, Zahid, Krishnaveni, Ghattu V., Kumaran, Kalyanaraman, Potdar, Ramesh D., Sahariah, Sirazul A., Krishna, Murali, Di Gravio, Chiara, Mali, Inder D, Sankareswaran, Alagu, Hussain, Akhtar, Bhowmik, Biswajit W, Khan, Abdul Kalam A., Knight, Bridget A., Frayling, Timothy M., Finer, Sarah, Fall, Caroline, Yajnik, Chittaranjan S., Freathy, Rachel M., Hitman, Graham A. and Chandak, Giriraj R. (2022) Babies of South Asian and European ancestry show similar associations with genetic risk score for birth weight despite the smaller size of South Asian newborns. Diabetes, 71 (4), 821-836. (doi:10.2337/db21-0479).

Record type: Article

Abstract

Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from these cohorts were compared with South Asians in UK Biobank and the Exeter Family Study of Childhood Health, a European ancestry cohort. Birth weight increased by 50.7 g and 33.6 g per SD of fGS (P = 9.1 × 10-11) and mGS (P = 0.003), respectively, in South Asians. A relatively weaker mGS effect compared with Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birth weight was strongly associated with body size in both childhood and adolescence (P = 3 × 10-5 to 1.9 × 10-51); however, fGS was associated with body size in childhood only (P < 0.01) and with head circumference, fasting glucose, and triglycerides in adults (P < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birth weight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status, etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism that partly explains associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians.

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Accepted/In Press date: 11 January 2022
e-pub ahead of print date: 21 January 2022
Published date: 1 April 2022
Additional Information: Publisher Copyright: © 2022 by the American Diabetes Association.

Identifiers

Local EPrints ID: 454374
URI: http://eprints.soton.ac.uk/id/eprint/454374
ISSN: 0012-1797
PURE UUID: bce1132a-fc14-407c-9613-50a03f0b06cb
ORCID for Caroline Fall: ORCID iD orcid.org/0000-0003-4402-5552

Catalogue record

Date deposited: 08 Feb 2022 17:41
Last modified: 17 Mar 2024 02:36

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Contributors

Author: Suraj N. Nongmaithem
Author: Robin N. Beaumont
Author: Akshay Dedaniya
Author: Andrew R. Wood
Author: Babatunji-William Ogunkolade
Author: Zahid Hassan
Author: Ghattu V. Krishnaveni
Author: Ramesh D. Potdar
Author: Sirazul A. Sahariah
Author: Murali Krishna
Author: Chiara Di Gravio
Author: Inder D Mali
Author: Alagu Sankareswaran
Author: Akhtar Hussain
Author: Biswajit W Bhowmik
Author: Abdul Kalam A. Khan
Author: Bridget A. Knight
Author: Timothy M. Frayling
Author: Sarah Finer
Author: Caroline Fall ORCID iD
Author: Chittaranjan S. Yajnik
Author: Rachel M. Freathy
Author: Graham A. Hitman
Author: Giriraj R. Chandak

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