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.

Mitochondrial genome variations, mitochondrial‐nuclear compatibility, and their association with metabolic diseases

“…The possibility to meaningfully include environmental and nutritional factors as covariates in the analysis of gene × environment interactions currently remains highly challenging because of scarcity and complexity of the required data. These aspects and potentially statistically underpowered study designs could be the reason for apparently contradictory findings, such as haplogroup J supposedly being associated with decreased or increased risk of obesity in Caucasian or non‐Caucasian populations, respectively (28,32). Besides taking into account nongenetic factors, great potential will lie in combining mitochondrial haplogroup classifications with approaches to capture human genetic variation by nuclear haplotype analyses (92).…”

“…In non‐Caucasian populations, Qatari patients were found to have a twofold increased risk of obesity when belonging to haplogroup J and a lower risk when belonging to haplogroup X (32). In the Kuwait Arab population, the H2a haplogroup reduced the probability of having obesity (33).…”

The Mitochondrial tRNAPhe 625G>A Mutation in Three Han Chinese Families With Cholecystolithiasis

“…The specific mtDNA background B5a1 was significantly associated with Southeast Asian G11778A LHON and appeared to modify the risk of visual loss ( Kaewsutthi et al, 2011 ). Mitochondrial haplogroup J was associated with a higher risk of obesity in the Qatari population( Dashti et al, 2021 ). Mitochondrial DNA Haplogroup M7 Confers Disability in a Chinese Aging Population( Sun et al, 2020 ).…”

Heterogeneity in biomarkers, mitogenome and genetic disorders of Arab population with special emphasis on large-scale whole-exome sequencing

“…SNPs [159]. The report from Emirati population showed that the Arab population received sufficient gene flow from African ancestries.…”