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

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 birthweight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic score (fGS) and maternal genetic score (mGS) from 196 birthweight-associated variants identified in Europeans and conducted association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6 years' intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from above cohorts were compared with South Asians in UK BioBank and The Exeter Family Study of Childhood Health, a European ancestry cohort. Birthweight increased by 50.7g and 33.6g per standard deviation of fGS (p = 9.1×10-11) and mGS (p = 0.003) respectively in South Asians. A relatively weaker maternal genetic score effect compared to Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birthweight was strongly associated with body size in both childhood and adolescence (p = 3×10-5 - 1.9×10-51), however, fetal genetic score 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 birthweight 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 partly explaining 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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“… 45 , 48 , 49 , 50 We have reported a substantially lower birthweight in neonates from Indian subcontinent compared to neonates from UK at comparable birthweight GRS. 51 Lower birthweight is a risk factor for future diabetes and other cardiometabolic outcomes. Thus, the population-based differences could extend beyond genetics in that Indians and Europeans have very different life-course experiences.…”

Economic Evaluation: Costing participatory learning and action cycles with women’s groups to improve feeding, care and dental hygiene for South Asian infants in London

“…Evidence suggests that a significant proportion of the minority ethnic population in the UK, especially those of South Asian heritage, experience substantial social and economic disadvantage, which may contribute to poorer health outcomes [13,14] . Children from South Asian families residing in the UK are susceptible to many of the same developmental risks as young children residing in South Asia, including poorer birth outcomes and nutritional status [15,16] . The causes of these risks in the UK context are complex but include socioeconomic deprivation, discrimination, language difficulties, cultural norms, and a lack of access to health information, among other factors [17] .…”

“…Children from South Asian families residing in the UK are susceptible to many of the same developmental risks as young children residing in South Asia, including poorer birth outcomes and nutritional status [15,16] . The causes of these risks in the UK context are complex but include socioeconomic deprivation, discrimination, language difficulties, cultural norms, and a lack of access to health information, among other factors [17] .…”