Genome- and epigenome-wide association study of hypertriglyceridemic waist in Mexican American families

Authors

Manju Mamtani, The University of Texas Rio Grande Valley
Hemant Kulkarni, The University of Texas Rio Grande Valley
Thomas D. Dyer, The University of Texas Rio Grande Valley
Harald H. H. Goring, The University of Texas Rio Grande Valley
Jennifer L. Neary
Shelley A. Cole
Jack W. Kent Jr.
Satish Kumar, The University of Texas Rio Grande Valley
David C. Glahn
Michael C. Mahaney, The University of Texas Rio Grande Valley
Anthony G. Comuzzie
Laura Almasy, The University of Texas Rio Grande Valley
Joanne E. Curran, The University of Texas Rio Grande Valley
Ravindranath Duggirala, The University of Texas Rio Grande Valley
John Blangero, The University of Texas Rio Grande Valley
Melanie A. Carless

Document Type

Article

Publication Date

1-2016

Abstract

Background: There is growing interest in the hypertriglyceridemic waist (HTGW) phenotype, defined as high waist circumference (≥95 cm in males and ≥80 cm in females) combined with high serum triglyceride concentration (≥2.0 mmol/L in males and ≥1.5 mmol/L in females) as a marker of type 2 diabetes (T2D) and cardiovascular disease. However, the prevalence of this phenotype in high-risk populations, its association with T2D, and the genetic or epigenetic influences on HTGW are not well explored. Using data from large, extended families of Mexican Americans (a high-risk minority population in the USA) we aimed to: (1) estimate the prevalence of this phenotype, (2) test its association with T2D and related traits, and (3) dissect out the genetic and epigenetic associations with this phenotype using genome-wide and epigenome-wide studies, respectively.

Results: Data for this study was from 850 Mexican American participants (representing 39 families) recruited under the ongoing San Antonio Family Heart Study, 26 % of these individuals had HTGW. This phenotype was significantly heritable (h2r = 0.52, p = 1.1 × 10−5) and independently associated with T2D as well as fasting glucose levels and insulin resistance. We conducted genome-wide association analyses using 759,809 single nucleotide polymorphisms (SNPs) and epigenome-wide association analyses using 457,331 CpG sites. There was no evidence of any SNP associated with HTGW at the genome-wide level but two CpG sites (cg00574958 and cg17058475) in CPT1A and one CpG site (cg06500161) in ABCG1 were significantly associated with HTGW and remained significant after adjusting for the closely related components of metabolic syndrome. CPT1A holds a cardinal position in the metabolism of long-chain fatty acids while ABCG1 plays a role in triglyceride metabolism.

Conclusions: Our results reemphasize the value of HTGW as a marker of T2D. This phenotype shows association with DNA methylation within CPT1A and ABCG1, genes involved in fatty acid and triglyceride metabolism. Our results underscore the importance of epigenetics in a clinically informative phenotype.

Recommended Citation

Mamtani, M., Kulkarni, H., Dyer, T.D. et al. Genome- and epigenome-wide association study of hypertriglyceridemic waist in Mexican American families. Clin Epigenet 8, 6 (2016). https://doi.org/10.1186/s13148-016-0173-x

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Clinical Epigenetics

DOI

10.1186/s13148-016-0173-x

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics