Genetic variants associated with spontaneous preterm birth in women from India: a prospective cohort study

Background Despite having the highest number of preterm births globally, no genomic study on preterm birth was previously published from India or other South-Asian countries.Methods We conducted a genome-wide association (GWA) study of spontaneous preterm birth (sPTB) on 6211 women from India. We used a novel resampling procedure to identify the associated single nucleotide polymorphisms (SNPs) followed by haplotype association analysis and imputation.Findings We found that 512 maternal SNPs were associated with sPTB (p < 2.51e-3), of which minor allele at 19 SNPs (after Bonferroni correction) had increased genotype relative risk. Haplotypes containing six of the 19 SNPs (rs13011430, rs8179838, rs2327290, rs4798499, rs7629800, and rs13180906) were associated with sPTB (p < 9.9e-4; Bonferroni adjusted p-value <0.05). After imputation in regions around the 19 SNPs, 15 imputed SNPs were found to be associated with sPTB (Bonferroni adjusted p-value <0.05). One of these imputed SNPs, rs35760881, and three other SNPs (rs17307697, rs4308815, and rs10983507) were also reported to be associated with sPTB in women belonging to European ancestry. Moreover, we found that GG genotype at rs1152954, one of the associated SNPs, enhanced risk of sPTB and reduced telomere length.Interpretation This is the first study from South Asia on the genome-wide identification of maternal SNPs associated with sPTB. These SNPs are known to alter the expression of genes associated with major pathways in sPTB viz. inflammation, apoptosis, cervical ripening, telomere maintenance, selenocysteine biosynthesis, myometrial contraction, and innate immunity. From a public health perspective, the trans-ethnic association of four SNPs identified in our study may help to stratify women with risk of sPTB in most populations.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).