Childhood BMI and Adult Type 2 Diabetes, Coronary Artery Diseases, Chronic Kidney Disease, and Cardiometabolic Traits: A Mendelian Randomization Analysis

Literature - Geng T, Smith CE, Li C, et al. - Diabetes Care 2018; published online ahead of print

Background

Observational studies show that a higher body-mass-index (BMI) during childhood is associated with an increased risk of cardio-metabolic diseases later in life [1,2]. Mendelian randomization (MR) analyses show that there is a causal association between adult obesity and coronary artery disease (CAD), type 2 diabetes (T2DM), and cardio-metabolic traits in midlife [3,4], but the causal effect of childhood obesity on these outcomes in adults is not known.

In this MR analysis, the causal effect of childhood BMI on adult T2DM, CAD, and chronic kidney disease (CKD) was examined. Moreover, the causal effect of childhood BMI on adult levels of cardio-metabolic traits, such as anthropometrics, glycemic traits, and lipids was evaluated.

For this purpose, 15 single nucleotide polymorphisms (SNPs; P<5x10-8) were identified from genome-wide association studies (GWAS) by the Early Growth Genetics (EGG) consortium, and a genetic risk score was created that summed the number of BMI-increasing alleles weighted based on their β. The genetic risk score was strongly associated with childhood BMI (P=3.12x10-10), and explained 2.0% of the variance in childhood BMI [5].

Main results

• None of the SNPs was found to be in linkage disequilibrium (LD) with each other at an r2 > 0.05, and the results were not influenced by pleiotropy.
• A one-SD increase in childhood BMI (kg/m2) was associated with a substantial increase in risk of T2DM, ranging from 47% (95%CI: 1.18-1.82; P=4.0x10-4) to 83% (95%CI: 1.46-2.30; P=2.5x10-7) dependent on the MR method used, and a 28% increase in risk of CAD (95%CI: 1.17-1.39; P=2.1x10-8).
• Childhood BMI was not associated with adult CKD (OR: 1.14; 95%CI: 0.99-1.31; P=0.076).

A one-SD increase in childhood BMI was causally associated with a:

• 0.587-SD increase in BMI (β: 0.587; 95%CI: 0.458-0.716; P=4.9x10-18)
• 0.062-SD increase in hip circumference adjusted BMI (β: 0.062; 95%CI: 0.025-0.099; P=0.001)
• 0.602-SD increase in waist circumference adjusted BMI (β: 0.602; 95%CI: 0.370-0.834; P=4.8x10-7)
• 0.111 pmol/L increase in log fasting insulin (β: 0.111; 95%CI: 0.065-0.157; P=2.7x10-6)
• 0.068 increase in log HOMA-B (β: 0.068; 95%CI: 0.026-0.110; P = 0.001)
• 0.126 increase in log HOMA-IR (β: 0.126; 95%CI: 0.085-0.168; P=4.7x10-9)
• 0.109-SD increase in triglycerides (β: 0.109; 95%CI: 0.058-0.160; P=3.0x10-5)
• 0.138-SD decrease in HDL (β: 20.138; 95%CI: 20.207-20.069; P=9.3x10-5)

Conclusion

References

Find this article online at Diabetes Care 2018