Document Type
Article
Publication Title
JAMA Network Open
Abstract
Importance The fat mass and obesity–associated gene (FTO) is associated with obesity phenotypes, but the association is inconsistent across populations. Within-population differences may explain some of the variability observed.
Objective To investigate sex differences in the association between FTO single-nucleotide variants (SNVs) and obesity traits among self-identified non-Hispanic Black and non-Hispanic White US adults, to examine whether the SNVs were associated with cardiometabolic diseases, and to evaluate whether obesity mediated the association between FTO SNVs and cardiometabolic diseases.
Design, Setting, and Participants This cross-sectional study used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a US population-based cohort study with available genetic data (assayed in 2018) and phenotypic data at baseline (enrolled 2003-2007). Participants were aged 45 to 98 years at baseline. Data were analyzed from October 2021 to October 2022.
Exposures Eleven SNVs in the FTO gene present among both Black and White participants.
Main Outcomes and Measures Objectively measured obesity indicators (body mass index and waist-to-height ratio), objectively measured and/or self-reported cardiometabolic diseases (hypertension, stroke history, heart disease, and diabetes), and self-reported social-economic and psychosocial status.
Results A total of 10 447 participants (mean [SD] age, 64.4 [9.7] years; 5276 [55.8%] women; 8743 [83.7%] Black and 1704 [16.3%] White) were included. In the White group, 11 FTO SNVs were significantly associated with obesity, hypertension, and diabetes using linear models (eg, body mass index: β = 0.536; 95% CI, 0.197-0.875), but none of the FTO SNVs were associated with obesity traits in the Black group. White males had a higher risk of obesity while White females had a higher risk of hypertension and diabetes. However, 1 FTO SNV (rs1121980) was associated with a direct increase in the risk of heart disease in Black participants not mediated by obesity (c′ = 0.145 [SE, 0.0517]; P = .01).
Conclusions and Relevance In this cross-sectional study of obesity phenotypes and their association with cardiometabolic diseases, the tested FTO SNVs reflected sex differences in White participants. Different patterns of associations were observed among self-identified Black participants. Therefore, these results could inform future work discovering risk alleles or risk scores unique to Black individuals or further investigating genetic risk in all US residents.
DOI
https://doi.org/10.1001/jamanetworkopen.2023.47171
Publication Date
12-8-2023
PubMed ID
PMID: 38064210; PMCID: PMC10709778
College or School
School of Public Health
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Supplemental Associated Link
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812716
Recommended Citation
Yu H, Armstrong N, Pavela G, Kaiser K. Sex and Race Differences in Obesity-Related Genetic Susceptibility and Risk of Cardiometabolic Disease in Older US Adults. JAMA Netw Open. 2023 Dec 1;6(12):e2347171. doi: 10.1001/jamanetworkopen.2023.47171. PMID: 38064210; PMCID: PMC10709778.
Supplemental Data
APC_2024_04_Yu_supp2.pdf (239 kB)
Data disclosure
Comments
2023/2024 APC Fund Awardee:
Dr. Kathryn Kaiser, Assistant Professor
UAB School of Public Health
Award Amount: $2,000.00