Higher childhood BMI associated with increased risk of cardio-metabolic disease later in life

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


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)


A genetic predisposition to higher childhood BMI was associated with an increased risk of T2DM, CAD, and cardio-metabolic traits in adult life. These results show that there is a substantial public health impact of childhood BMI modification.


1. Litwin SE. Childhood obesity and adulthood cardiovascular disease: quantifying the lifetime cumulative burden of cardiovascular risk factors. J Am Coll Cardiol 2014;64:1588–1590

2. JuonalaM, Magnussen CG, Berenson GS, et al. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 2011;365:1876–1885

3. Dale CE, Fatemifar G, Palmer TM, et al.; UCLEB Consortium; METASTROKE Consortium. Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes,andtype2diabetesmellitus:a Mendelian randomization analysis. Circulation 2017;135:2373–2388

4. Emdin CA, Khera AV, Natarajan P, et al. Genetic association of waist-to-hip ratio with cardiometabolic traits, type 2 diabetes, and coronary heart disease. JAMA 2017;317:626–634

5. Felix JF, Bradfield JP, Monnereau C, et al. Bone Mineral Density in Childhood Study (BMDCS); Early Genetics and Lifecourse Epidemiology (EAGLE) consortium; Early Growth Genetics (EGG) Consortium; BoneMineral Density in Childhood Study BMDCS. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Hum Mol Genet 2016;25:389–403

Find this article online at Diabetes Care 2018

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