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Case subjects with type 2 diabetes were diagnosed according to the 1999 World Health Organization criteria of fasting plasma glucose concentration ≥7.0 mmol/L or 2-h plasma glucose concentration ≥11.1 mmol/L, by report of diabetes medication use, or based on medical record review ( 17).

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Data Sourcesįor disease outcomes, summary-level data were extracted from the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) consortium ( n = 149,821) ( 14) for type 2 diabetes ( Supplementary Table 1), the CKDGen consortium ( n = 133,413) ( 15) for CKD ( Supplementary Table 2), and the Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM) plus the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium (60,801 CAD case subjects and 123,504 control subjects) ( 16) for CAD ( Supplementary Table 3 and Supplementary Data). This score explained 2.0% of the variance in childhood BMI ( 13), thus validating assumption 1 ( Fig. The genetic risk score was strongly associated with childhood BMI ( P = 3.12 × 10 −10). The GWAS study combined these 15 genome-wide significant SNPs into a genetic risk score that summed the number of BMI-increasing alleles weighted based on their β.

In the case of twin pairs, only one twin was included, either randomly or based on genotyping or imputation quality ( 13).

Sex- and age-adjusted SD scores were created for childhood BMI at the latest time point (oldest age, if multiple measurements existed) the mean age was between 36.4 ± 0.7 and 120.0 ± 0.5 months. The specific study population is described in the Supplementary Data. All children included in this GWAS were of European ethnic origin and 53% of the children were Caucasian. This GWAS included 35,668 children from 20 studies in the discovery phase and 11,873 children from 13 studies in the replication phase ( 13). We used 15 single nucleotide polymorphisms (SNPs P < 5 × 10 −8) identified from previous genome-wide association studies (GWAS) by the Early Growth Genetics (EGG) consortium as an IV for childhood BMI.

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