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Predicting anthropometric and metabolic traits with a genetic risk score for obesity in a sample of Pakistanis.

ABSTRACT: Obesity is an outcome of multiple factors including environmental and genetic influences. Common obesity is a polygenic trait indicating that multiple genetic variants act synergistically to influence its expression. We constructed a genetic risk score (GRS) based on five genetic variants (MC4R rs17782313, BDNF rs6265, FTO rs1421085, TMEM18 rs7561317, and NEGR1 rs2815752) and examined its association with obesity-related traits in a sample of Pakistanis. The study involved 306 overweight/obese (OW/OB) and 300 normal-weight (NW) individuals. The age range of the study participants was 12-63 years. All anthropometric and metabolic parameters were measured for each participant via standard procedures and biochemical assays, respectively. The genetic variants were genotyped by allelic discrimination assays. The age- and gender-adjusted associations between the GRS and obesity-related anthropometric and metabolic measures were determined using linear regression analyses. The results showed that OW/OB individuals had significantly higher mean ranks of GRS than NW individuals. Moreover, a significant association of the GRS with obesity-related anthropometric traits was seen. However, the GRS did not appear to affect any obesity-related metabolic parameter. In conclusion, our findings indicate the combined effect of multiple genetic variants on the obesity-related anthropometric phenotypes in Pakistanis.

SUBMITTER: Rana S

PROVIDER: S-EPMC8050295 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundObesity is more prevalent in men than in women in China, especially within the middle-aged population.ObjectivesThe present study aims to determine the contribution of sexual dimorphisms to obesity and related traits in terms of the mechanisms involving the obesity-related genetic variants among patients of Chinese Han ancestry with type 2 diabetes.MethodIn the Chinese National Diabetes and Metabolic Disorders Study, 2,555 out of 4,036 patients with type 2 diabetes were treatment naive, including 1,142 men and 1,413 women. Single-nucleotide polymorphisms (SNP) from 18 genomic loci previously found to be associated with obesity-related traits were successfully genotyped, and a genetic risk score (GRS) was constructed by summing the risk alleles for obesity.ResultsSingle SNP analysis showed that genetic variants in SLC30A10, TMEM18, GNPDA2, PRL, TFAP2B, BDNF, MTCH2, FTO, and MC4R were nominally associated with waist circumference (WC), BMI, and risk for abdominal or general obesity in the untreated patients with type 2 diabetes, as well as in the total group of patients with type 2 diabetes (untreated and treated) (p < 0.05). Interactions between sex and SNP in PRL, MTCH2,and FTO were detected (p < 0.05). In the untreated patients with diabetes, the GRS was nominally associated with WC (β = 0.0032, SE = 0.0011; p = 0.003), BMI (β = 0.0030, SE = 0.0013; p = 0.027), and increased risk for abdominal (OR = 1.08; 95% CI 1.02-1.13; p = 0.004) or general obesity (OR = 1.07; 95% CI 1.02-1.13; p = 0.011) in men but not in women. GRS-sex interactions were detected in the determinant of WC (p = 0.019) and abdominal obesity (p = 0.016). Among patients aged 30-60 years, GRS was found to be significantly associated with WC (β = 0.0050, SE = 0.0016; p = 0.002) and abdominal obesity (OR = 1.10; 95% CI 1.04-1.17; p = 0.001) and nominally associated with BMI (β = 0.0057, SE = 0.0020; p = 0.005) and general obesity (OR = 1.07; 95% CI 1.01-1.14; p = 0.027) in men, whereas in women none of the associations were detected. GRS-sex interactions were present in the determinant of WC (p = 0.015), BMI (p = 0.032), and abdominal obesity (p = 0.012). Among patients aged 60 years or older, neither an association of GRS with obesity-related traits nor GRS-sex interactions were detected.ConclusionsGenetic factors contribute to obesity-related traits in a sex-dependent pattern among middle-aged Chinese, and men tend to be more susceptible to the genetic risk of obesity.

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Predicting anthropometric and metabolic traits with a genetic risk score for obesity in a sample of Pakistanis.

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