Science Advances

Supplementary Materials

The PDF file includes:

  • Legends for tables S1 and S2
  • Table S3. The SNP selection criteria used for selecting loci from stage 1 GWAS meta-analysis data and proxies used for follow-up in stage 2.
  • Legends for tables S4 and S5
  • Table S6. Conditional analysis in the NFBC1966 data (N = 2585) of the BMI-AP association with the lead GWAS SNP rs9436303 adjusting for the early-onset obesity SNP rs11208659.
  • Legend for table S7
  • Table S8. Biological and functional mechanisms of the nearest genes to the four genome-wide significant SNPs.
  • Table S9. Top eQTLs (FDR < 1%) in five ex vivo tissues in high LD (R2 > 0.8) with the lead GWAS SNPs in LEPR/LEPROT locus.
  • Table S10. Direct lookup on eQTL (P < 0.001) data in five ex vivo tissues of the lead GWAS SNPs in LEPR/LEPROT locus.
  • Legends for tables S11 and S12
  • Table S13. The directional consistency between phenotypic and genetic correlations for the same trait.
  • Legends for tables S14 and S15
  • Table S16. Gene set enrichment analysis (MAGENTA) of biological pathways based on the discovery GWAS.
  • Table S17. Detailed description of IGF-1 signaling pathway associated with AGE-AR (FDR < 0.05) in MAGENTA gene set enrichment analysis.
  • Legends for tables S18 and S19
  • Fig. S1. Graphical illustration of height and weight growth patterns and the derived measures of early growth traits used in the present study.
  • Fig. S2. Summary of study design.
  • Fig. S3. The participating studies with their geographical location.
  • Fig. S4. The Manhattan plot and quantile-quantile plot of the association P values for the six early growth phenotypes from stage 1 genome-wide association analyses.
  • Fig. S5. Regional association and forest plots of the three genome-wide significant loci associated with early growth traits that have been previously linked with adult BMI.
  • Fig. S6. Heterogeneity analyses of the GWAS lead SNP rs9436303 at LEPR/LEPROT locus.
  • Fig. S7. Regional plots of the GWAS and GTEx cis-eQTL data used in the colocalization analysis of the early growth–associated loci.
  • Fig. S8. Tissue-specific PPs of colocalization of TFAP2B.
  • Fig. S9. Genomic annotation analysis of the colocalized variants involved in the regulation of LEPR, LEPROT, and TFAP2B gene expression.
  • Fig. S10. Adult BMI GRS analysis of early growth traits.
  • Note S1. Literature search for epidemiological associations between early growth traits and childhood and adult traits.
  • Note S2. Cohort description (see also tables S1 and S2 for genotyping details and figs. S1 to S3).
  • Note S3. Funding and acknowledgments by the study.
  • References (61104)

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Other Supplementary Material for this manuscript includes the following:

  • Table S1 (Microsoft Excel format). Study characteristics, exclusions, genotyping, quality control, and imputation of stage 1 studies.
  • Table S2 (Microsoft Excel format). Study characteristics, exclusions, genotyping, and quality control in stage 2 studies.
  • Table S4 (Microsoft Excel format). The association of the four genome-wide significant SNPs or proxies in high LD (R2 > 0.8) with other phenotypes in published GWASs retrieved from PhenoScanner database.
  • Table S5 (Microsoft Excel format). The association of the four genome-wide significant SNPs with other phenotypes in the Gene Atlas PheWAS on the UK Biobank data.
  • Table S7 (Microsoft Excel format). Variant effect prediction of the four genome-wide significant SNPs.
  • Table S11 (Microsoft Excel format). Direct lookup of the lead GWAS SNPs in LEPR/LEPROT and TFAP2B locus on methylation QTL (FDR < 1%) in blood drawn at five different life stages: mother’s pregnancy (~29.2 years, SD = 4.4 years) and middle age (~47.5 years, SD = 4.5 years), and offspring’s birth (0 years), childhood (~7.5 years, SD = 0.15 years), and adolescence (~17.1 years, SD = 1.0 years).
  • Table S12 (Microsoft Excel format). Cross-trait genetic correlations between five early growth traits and 80 other GWAS phenotypes from LD score regression analyses.
  • Table S14 (Microsoft Excel format). Lookup of the GIANT consortium BMI-associated SNPs on the stage 1 GWAS meta-analyses of the six early growth traits.
  • Table S15 (Microsoft Excel format). The GRS of adult BMI using SNP weights from the GIANT consortium applied to the early growth trait summary statistics from the stage 1 GWAS meta-analyses.
  • Table S18 (Microsoft Excel format). SNP heritability of the early growth traits estimated with SumHer and LD score.
  • Table S19 (Microsoft Excel format). Individual contributions of authors.

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