Mitochondrial haplogroup J associated with higher risk of obesity in the Qatari population

Abstract

Obesity, a major risk factor for metabolic disorders, is highly prevalent in Qatari population. Maternal transmission of obesity traits can be significant; for example, X haplogroup is known to be associated with lower BMI and body fat mass in Northern Europeans and T haplogroup which is a sister haplogroup of J is known to be associated with obesity in Caucasian subjects from Austria and Southern Italy. We aimed to delineate the mitochondrial haplogroups and variants associated with obesity in Qatari population. Mitochondrial genomes of 864 Qatari individuals were extracted from whole exome sequencing data with an average coverage of 77X. We distributed the participants into 2 sub-cohorts: obese (BMI ≥ 30) and non-obese (BMI < 30); the mean value of BMI from these two groups were 36.5 ± 5.7 and 26.5 ± 2.6, respectively. Mitochondrial haplogroup profiling followed by uni- and multivariant association tests adjusted for covariates were performed. Qatari individuals with mitochondrial haplogroup J had an increased (twofold) risk of obesity (odds ratio [OR] 1.925; 95% CI 1.234-3.002; P = 0.0038; the Bonferroni adjusted P value threshold is 0.0041), whereas the individuals with haplogroup X were at low risk of obesity (OR 0.387; 95% CI 0.175-0.857; P = 0.019). Further, a set of 38 mitochondrial variants were found to be associated (at P ≤ 0.05) with obesity in models adjusted for age, sex and haplogroup.

Figure 1

Average coverage of 864 Qatari sample across the whole mtDNA using whole exome sequencing data.

Figure 2

Frequencies of mitochondrial haplogroups observed in the 864 Qatari samples.

Figure 3

Principal component analysis of the 864 Qatari samples based on their mtDNA. (A) Obesity status was considered: the blue color represents the non-obese individuals and the red color represents the obese individuals. (B) Haplogroup profiling was considered. PC1 and PC2 on x- and y-axis represent Principal component 1 and Principal component 2 and their variations in percentage, respectively.

Figure 4

Distribution of major mtDNA haplogroups frequency in obese and non-obese groups.

Figure 5

Quantile–quantile plots of the expected and observed − log(p-values) for the association of mitochondrial variants with obesity (λ = 1.0035) upon correction for age, sex and haplogroups.