Bhattacharjee Esha, Thiruvengadam Ramachandran, Das Chitrarpita, Wadhwa Nitya, Natchu Uma Chandra Mouli, Kshetrapal Pallavi, Bhatnagar Shinjini, Majumder Partha Pratim, Maitra Arindam
National Institute of Biomedical Genomics, PO: NSS, Kalyani, India.
Regional Centre for Biotechnology, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad, India.
Lancet Reg Health Southeast Asia. 2023 Apr 18;14:100190. doi: 10.1016/j.lansea.2023.100190. eCollection 2023 Jul.
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.
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.
We found that 512 maternal SNPs were associated with sPTB ( < 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 ( < 9.9e-4; Bonferroni adjusted -value <0.05). After imputation in regions around the 19 SNPs, 15 imputed SNPs were found to be associated with sPTB (Bonferroni adjusted -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.
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.
Department of Biotechnology (India), Grand Challenges India - All Children Thriving Program and Biotechnology Industry Research Assistance Council (BIRAC).
尽管印度是全球早产数量最多的国家，但此前印度或其他南亚国家尚未发表过关于早产的基因组学研究。
我们对来自印度的6211名女性进行了自发性早产（sPTB）的全基因组关联（GWA）研究。我们使用了一种新颖的重采样程序来识别相关的单核苷酸多态性（SNP），随后进行单倍型关联分析和基因填充。
我们发现512个母体SNP与sPTB相关（P < 2.51e-3），其中19个SNP的次要等位基因（经过Bonferroni校正后）具有增加的基因型相对风险。包含19个SNP中的6个（rs13011430、rs8179838、rs2327290、rs4798499、rs7629800和rs13180906）的单倍型与sPTB相关（P < 9.9e-4；Bonferroni校正后的P值<0.05）。在对19个SNP周围区域进行基因填充后，发现15个填充后的SNP与sPTB相关（Bonferroni校正后的P值<0.05）。其中一个填充后的SNP，rs35760881，以及其他三个SNP（rs17307697、rs4308815和rs10983507）在欧洲血统的女性中也被报道与sPTB相关。此外，我们发现相关SNP之一rs1152954处的GG基因型会增加sPTB的风险并缩短端粒长度。
这是南亚地区第一项关于全基因组识别与sPTB相关的母体SNP的研究。已知这些SNP会改变与sPTB主要途径相关的基因表达，即炎症、细胞凋亡、宫颈成熟、端粒维持、硒代半胱氨酸生物合成、子宫肌层收缩和先天免疫。从公共卫生的角度来看，我们研究中确定的四个SNP的跨种族关联可能有助于在大多数人群中对有sPTB风险的女性进行分层。
生物技术部（印度）、印度大挑战 - 所有儿童茁壮成长计划和生物技术产业研究援助理事会（BIRAC）。
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