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Additional file 1: Supplementary Table 1. Association results of individual T2D SNPs used as genetic instruments in Mendelian randomization for their association with T2D. Supplementary Table 2. Association of individual T2D SNPs used as genetic instruments in Mendelian randomization analyses for their association with 25(OH)D concentrations. Supplementary Table 3. Association results of individual vitamin D SNPs used as genetic instruments in Mendelian randomization for their association with circulating 25(OH)D concentration. Supplementary Table 4. Association results of individual vitamin D SNPs used as genetic instruments in Mendelian randomization for their association with T2D. Supplementary Table 5. Association of vitamin D SNPs used as genetic instruments for affecting 25(OH)D concentrations using UV index as a covariate. Supplementary Table 6. Association of vitamin D SNPs used as genetic instruments showing their effect on Type 2 diabetes risk using UV index as a covariate. Supplementary Table 7 A-B. Results of joint metanalysis of current study and a published study (Lu et al, 2018) showing significant associations of variants in vitamin D candidate genes (GC and DHCR7) for effecting 25(OH)D concentrations. Supplementary Table 8 A-B. Results of joint metanalysis of current study and a published study (Lu et al, 2018) showing effects of genetically instrumented vitamin D candidate genes (GC and DHCR7) SNPs for their effects on T2D risk. Supplementary Table 9. Information on samples with missing 25(OH)D levels from 8 different cohorts. Supplementary Table 10. Differences in latitude, 25(OH)D concentration and distribution of allele frequencies of vitamin D and T2D SNPs among South Asian and European cohorts.

Additional file 3. Online Supplemental Information: Phenotypic measurements including T2D, 25(OH)D, and other recruitment details are presented separately for each cohort.

Additional file 2: Supplementary (Flow Chart). Experimental plan including the details of participating cohorts and candidate gene SNPs used as genetic instrument for performing a bidirectional Mendelian randomization study. Supplementary Figure 1 (A-B). Association analysis of composite gene score of T2D SNPs (IGF2BP2, TCF7L2 and KCNQ1) used as a genetic instrument for their joint effect on T2D and 25(OH)D concentrations ( https://www.graphpad.com/scientific-software/prism/ ). Supplementary Figure 2 (A-B). Association analysis of composite gene score of vitamin D SNPs (GC, CYP2R1 and DHCR7) used as a genetic instrument for their effect on 25(OH)D concentrations and T2D ( https://www.graphpad.com/scientific-software/prism/ ). Supplementary Figure 3. This figure illustrates pathways of synthesis, absorption, metabolism, and transportation of vitamin D. Genetic factors known to influence circulating levels of vitamin D are shown in the figure. DHCR7 expresses a reductase which uses nicotinamide adenine dinucleotide phosphate-oxidase to catalyzes the production of cholesterol to 7-dehydrocholesterol (7-DHC). The GC gene catalyzes the vitamin D binding protein formation. The enzyme (25-hydroxylase) responsible for the first hydroxylation step is encoded by CYP2R1. The enzyme in the kidneys responsible for the second hydroxylation is catalyzed by the CYP27B1 gene product (not used in this study). 1,25(OH)2D3 is the most effective and commonly measured vitamin D deficiency marker. Genetic instruments used in this study include gene pathways involved in vitamin D synthesis (DHCR7), metabolism (CYP2R1) and transport (GC) and genetic loci linked with increased T2D risk (IGF2BP2, TCF7L2, and KCNQ1). Note that in our results causality appears to be inferred by direct association of 25(OH)D variants (i.e. DHCR7) with 25(OH)D levels and the T2D phenotype. In contrast the T2D genes are associated with phenotype but not with the intermediate phenotype measured as 25(OH)D.

Low birth weight is one of the leading factors for infant morbidity and mortality. To a large extent affect, various maternal risk factors are associated with pregnancy outcomes by increasing odds of delivering an infant with low birth weight. Despite this association, understanding the maternal risk factors affecting term low birth weight has been a challenging task. To date, limited studies have been conducted in India that exert independent magnitude of these effects on term low birth weight. The aim of this review is to examine the current knowledge of maternal risk factors that contribute to term low birth weight in the Indian population. In order to identify the potentially relevant articles, an extensive literature search was conducted using PubMed, Goggle Scholar and IndMed databases (1993 – Dec 2020). Our results indi­cate that maternal age, educational status, socio-economic status, ethnicity, parity, pre-pregnancy weight, maternal stature, maternal body mass index, obstetric history, maternal anaemia, gestational weight gain, short pregnancy outcome, hypertension during pregnancy, infection, antepartum haemorrhage, tobacco consumption, maternal occupation, maternal psychological stress, alcohol consumption, antenatal care and mid-upper arm circumference have all independent effects on term low birth weight in the Indian pop­ulation. Further, we argue that exploration for various other dimensions of maternal factors and underlying pathways can be useful for a better understanding of how it exerts independent association on term low birth weight in the Indian sub-continent.