Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study

Abstract

Background: Childhood obesity is reported to be associated with the risk of many diseases in adulthood. However, observational studies cannot fully account for confounding factors. We aimed to systematically assess the causal associations between childhood body mass index (BMI) and various adult traits/diseases using two-sample Mendelian randomization (MR).

Methods: After data filtering, 263 adult traits genetically correlated with childhood BMI (P < 0.05) were subjected to MR analyses. Inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods were used to estimate the causal effects. Multivariable MR analysis was performed to test whether the effects of childhood BMI on adult traits are independent from adult BMI.

Results: We identified potential causal effects of childhood obesity on 60 adult traits (27 disease-related traits, 27 lifestyle factors, and 6 other traits). Higher childhood BMI was associated with a reduced overall health rating (β = - 0.10, 95% CI - 0.13 to - 0.07, P = 6.26 × 10^-11). Specifically, higher childhood BMI was associated with increased odds of coronary artery disease (OR = 1.09, 95% CI 1.06 to 1.11, P = 4.28 × 10^-11), essential hypertension (OR = 1.12, 95% CI 1.08 to 1.16, P = 1.27 × 10^-11), type 2 diabetes (OR = 1.36, 95% CI 1.30 to 1.43, P = 1.57 × 10^-34), and arthrosis (OR = 1.09, 95% CI 1.06 to 1.12, P = 8.80 × 10^-9). However, after accounting for adult BMI, the detrimental effects of childhood BMI on disease-related traits were no longer present (P > 0.05). For dietary habits, different from conventional understanding, we found that higher childhood BMI was associated with low calorie density food intake. However, this association might be specific to the UK Biobank population.

Conclusions: In summary, we provided a phenome-wide view of the effects of childhood BMI on adult traits. Multivariable MR analysis suggested that the associations between childhood BMI and increased risks of diseases in adulthood are likely attributed to individuals remaining obese in later life. Therefore, ensuring that childhood obesity does not persist into later life might be useful for reducing the detrimental effects of childhood obesity on adult diseases.

Keywords: Adult outcome; Causal; Childhood BMI; Mendelian randomization.

Fig. 1

a Schematic diagram of an MR analysis. Since genetic alleles are independently segregated and randomly assigned, SNPs are not associated with confounding factors that may bias estimates from observational studies. Three assumptions of MR are as follows: (1) the selected instrument is predictive of the exposure, (2) the instrument is independent of confounding factors, and (3) there is no horizontal pleiotropy (the instrument is associated with the outcome only through the exposure). b The analysis pipeline of the current study

Fig. 2

Summary view of the MR analysis results for the disease-related traits. Traits with significant positive associations with childhood BMI are shown in red. Traits with significant negative associations with childhood BMI are shown in blue. The other traits are shown in black. Traits from resources not specific to the UK Biobank population are shown in italic. For diseases from the UK Biobank population, those with pre-posed code (e.g., K80 Cholelithiasis) are obtained from clinical diagnoses. Diseases without pre-posed code were obtained from questionnaire. The URLs for detailed description for all phenotypes are listed in Additional file 1: Table S2

Fig. 3

Summary Mendelian randomization (MR) estimates derived from the inverse-variance weighted, MR-Egger, weighted median, and weighted mode-based methods for the 27 disease-related traits. Childhood BMI was used as exposure and significant associations were detected for these traits

Fig. 4

Summary view of the MR analysis results for the lifestyle factors and other traits. Traits with significant positive associations with childhood BMI are shown in red. Traits with significant negative associations with childhood BMI are shown in blue. The other traits are shown in black. Traits from resources not specific to the UK Biobank population are shown in italic. The URLs for detailed description for all phenotypes are listed in Additional file 1: Table S2

Fig. 5

Summary Mendelian randomization (MR) estimates derived from the inverse-variance weighted, MR-Egger, weighted median, and weighted mode-based methods for the 27 lifestyle factors and 6 other hematological test traits. Childhood BMI was used as exposure and significant associations were detected for these traits