Genetic risk score for adult body mass index associations with childhood and adolescent weight gain in an African population

Abstract

BackgroundNinety-seven independent single nucleotide polymorphisms (SNPs) are robustly associated with adult body mass index (BMI kg/m2) in Caucasian populations. The relevance of such variants in African populations at different stages of the life course (such as childhood) is unclear. We tested whether a genetic risk score composed of the aforementioned SNPs was associated with BMI from infancy to early adulthood. We further tested whether this genetic effect was mediated by conditional weight gain at different growth periods. We used data from the Birth to Twenty Plus Cohort (Bt20+), for 971 urban South African black children from birth to 18 years. DNA was collected at 13 years old and was genotyped using the Metabochip (Illumina) array. The weighted genetic risk score (wGRS) for BMI was constructed based on 71 of the 97 previously reported SNPs.ResultsThe cross-sectional association between the wGRS and BMI strengthened with age from 5 to 18 years. The significant associations were observed from 11 to 18 years, and peak effect sizes were observed at 13 and 14 years of age. Results from the linear mixed effects models showed significant interactions between the wGRS and age on longitudinal BMI but no such interactions were observed in sex and the wGRS. A higher wGRS was associated with an increased relative risk of belonging to the early onset obese longitudinal BMI trajectory (relative risk = 1.88; 95%CI 1.28 to 2.76) compared to belonging to a normal longitudinal BMI trajectory. Adolescent conditional relative weight gain had a suggestive mediation effect of 56% on the association between wGRS and obesity risk at 18 years.ConclusionsThe results suggest that genetic susceptibility to higher adult BMI can be tracked from childhood in this African population. This supports the notion that prevention of adult obesity should begin early in life. The genetic risk score combined with other non-genetic risk factors, such as BMI trajectory membership in our case, has the potential to be used to screen for early identification of individuals at increased risk of obesity and other related NCD risk factors in order to reduce the adverse health risk outcomes later.Electronic supplementary materialThe online version of this article (10.1186/s12263-018-0613-7) contains supplementary material, which is available to authorized users.

Interaction between Metabolic Genetic Risk Score and Dietary Fatty Acid Intake on Central Obesity in a Ghanaian Population

“…Our study is the first study of its kind, investigating the effect of different metabolic GRSs (the 12-, 8-and the 4-SNP GRS) on obesity-related traits in a Ghanaian population. We found that none of the metabolic GRSs were significantly associated with obesity-related traits in the Ghanaian population, which contradicts the findings of the previous GRS-related studies in European and African populations [15,[25][26][27][28][29][30]32,33]. Efforts to replicate previously reported genetic associations of individual SNPs with obesity measures in non-African populations have shown limited success among Africans [23,31,51,52], which is also in line with the findings from the present study.…”

“…A study among a rural population of Gambia demonstrated a positive association between a GRS of 28 SNPs and BMI and adult weight, whereas no association was found with the single SNP analysis [30,31]. Although genetic research in Africans is increasing in numbers [22], only a few studies have examined the association of GRS with obesity in Africa [30,32,33], which highlights the need for further research in African populations.…”

Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank

“…In a subset of 4,423 patients from the primary cohort with genome-wide association study (GWAS) data, we developed 6 different PRSs using published genetic variants associated with T2D, BMI, or response to OGLDs. We investigated the associations between glycemic progression and each PRS, including (1) European-T2D PRS derived from 143 single nucleotide polymorphisms (SNPs) identified in a meta-analysis of GWAS in European populations [4], (2) Asian-T2D PRS derived from 48 SNPs including those identified in Asian-GWAS or European SNPs replicated in East Asians [28], (3) BMI PRS derived from 97 SNPs associated with BMI [29,30], (4) metformin PRS derived from 8 SNPs associated with metformin response [6][7][8][9][10][11][12][13], (5) SU PRS derived from 7 SNPs associated with SU response [14][15][16][17][18], and (6) TZD PRS derived from 3 SNPs associated with TZD response [19][20][21]. All SNPs in PRS associated with BMI and drug responses were discovered in European populations.…”

Daily Branched‐Chain Amino Acid Intake and Risks of Obesity and Insulin Resistance in Children: A Cross‐Sectional Study

“…Many factors account for the rapid increase in pediatric obesity, including congenital and acquired factors. Maternal prepregnancy overweight and obesity and excess gestational weight gain are risk factors for children’s obesity; other childhood factors such as elevated energy intake, elevated screen time, and reduced outdoor activity also are risk factors for childhood obesity (22‐24). The present study indicated that daily dietary intake of BCAA was independently associated with increased risks for childhood overweight and insulin resistance after adjustment for these major risk factors.…”