The Influence of Obesity-Related Single Nucleotide Polymorphisms on BMI Across the Life Course
نویسندگان
چکیده
Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18-100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18-25 years), adulthood (ages 26-49 years), middle-age adulthood (ages 50-69 years), and older adulthood (ages ≥70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m², respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data.
منابع مشابه
Single Nucleotide Polymorphisms and Association Studies: A Few Critical Points
Uncovering DNA sequence variations that correlate with phenotypic changes, e.g., diseases, is the aim of sequence variation studies. Common types sequence variations are Single nucleotide polymorphism (SNP, pronounced snip).SNPs are the third-generation molecular marker. SNP represents a DNA sequence variant of a single base pair with the minor allele occurring in more than 1% of a given popula...
متن کاملOmentin-1 rs2274907 and resistin rs1862513 polymorphisms influence genetic susceptibility to nonalcoholic fatty liver disease
Nonalcoholic fatty liver disease (NAFLD) is an obesity-associated disease and dysregulation of adipokines has an important role in its development. Omentin-1 (ITLN1 protein) and resistin are two adipokine secreted from adipose tissue. Single nucleotide polymorphisms in the adipokine genes may affect expression and activity of the adipokine, and thus play a contributory role in NAFLD pathogenesi...
متن کاملProgressive influence of body mass index-associated genetic markers in rural Gambians
BACKGROUND In populations of European ancestry, the genetic contribution to body mass index (BMI) increases with age during childhood but then declines during adulthood, possibly due to the cumulative effects of environmental factors. How the effects of genetic factors on BMI change with age in other populations is unknown. SUBJECTS AND METHODS In a rural Gambian population (N=2535), we used ...
متن کاملPrognostic Significance of MMP2 and MMP9 Functional Promoter Single Nucleotide Polymorphisms in Head and Neck Squamous Cell Carcinoma
Objective(s) Matrix metalloproteinases comprise a family of enzyme that is able to degrade components of extra cellular matrix. There are single nucleotide polymorphisms in the promoter regions of several genes with ability to influence cancer susceptibility. The aim of this study was to analyses association between MMP2 and MMP9 promoter polymorphisms and head and neck squamous cell carcinoma...
متن کاملThe miR526b-5p-Related Single Nucleotide Polymorphisms, rs72618599, Located in 3\'-UTR of TCF3 Gene, is Associated with the Risk of Breast and Gastric Cancers
Introduction: Single nucleotide polymorphisms result in dysregulation of the proto-oncogene TCF3 gene, which is associated with the development, metastasis, and chemoresistance of different malignancies. Methods: GSE10810 microarray dataset and GEPIA2 online software were used to find differentially expressed genes and the TCF3 status in breast cancer (BC) and gastric cancer (GC), respectively....
متن کامل