Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;81(4):556-563.
doi: 10.1136/annrheumdis-2021-221635. Epub 2021 Dec 2.

Impact of adiposity on risk of female gout among those genetically predisposed: sex-specific prospective cohort study findings over >32 years

Natalie McCormick #  1   2   3 , Chio Yokose #  3   4 , Na Lu  2   5 , Amit D Joshi  3   6 , Gary C Curhan  5   7 , Hyon K Choi  8   9
Affiliations

Impact of adiposity on risk of female gout among those genetically predisposed: sex-specific prospective cohort study findings over >32 years

Natalie McCormick et al. Ann Rheum Dis. 2022 Apr.

Abstract

Objectives: To evaluate the joint (combined) association of excess adiposity and genetic predisposition with the risk of incident female gout, and compare to their male counterparts; and determine the proportion attributable to body mass index (BMI) only, genetic risk score (GRS) only, and to their interaction.

Methods: We prospectively investigated potential gene-BMI interactions in 18 244 women from the Nurses' Health Study and compared with 10 888 men from the Health Professionals Follow-Up Study. GRS for hyperuricaemia was derived from 114 common urate-associated single nucleotide polymorphisms.

Results: Multivariable relative risk (RR) for female gout was 1.49 (95% CI 1.42 to 1.56) per 5 kg/m2 increment of BMI and 1.43 (1.35 to 1.52) per SD increment in the GRS. For their joint association of BMI and GRS, RR was 2.18 (2.03 to 2.36), more than the sum of each individual factor, indicating significant interaction on an additive scale (p for interaction <0.001). The attributable proportions of joint effect for female gout were 42% (37% to 46%) to adiposity, 37% (32% to 42%) to genetic predisposition and 22% (16% to 28%) to their interaction. Additive interaction among men was smaller although still significant (p interaction 0.002, p for heterogeneity 0.04 between women and men), and attributable proportion of joint effect was 14% (6% to 22%).

Conclusions: While excess adiposity and genetic predisposition both are strongly associated with a higher risk of gout, the excess risk of both combined was higher than the sum of each, particularly among women.

Keywords: crystal arthropathies; epidemiology; gout.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE form for competing interests disclosure. NM, CY, NL and ADJ have no competing interests to declare. HC reports research support from Ironwood and Horizon, and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa and Vaxart. GC reports research support from Decibel Therapeutics, consulting fees from AstraZeneca, Allena Pharmaceuticals, Shire/Takeda, Dicerna and Orfan, and is the Chief Medical Officer at OM1.

Figures

1.
1.. Joint Association of Body Mass Index (BMI) and Genetic Predisposition on the Risk of Incident Gout.
GRS=genetic risk score; HPFS=Health Professionals Follow-Up Study; NHS=Nurses Health Study; NHS II=Nurses Health Study II. Normal weight = BMI <25 kg/m2; Overweight = 30<BMI ≥ 25 kg/m2; Obese = BMI ≥30 kg/m2
2.
2.. Joint Association of Body Mass Index (BMI) and Genetic Risk Score (GRS) on the Risk of Incident Gout.
HPFS=Health Professionals Follow-Up Study; NHS=Nurses Health Study; NHS II=Nurses Health Study II; SD=standard deviation. The area of each coloured bar represents the proportion of the excess risk of incident gout attributable to each individual exposure (BMI and GRS) and to their joint effects.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. American Journal of Medicine 2012;125(7):679–87 e1. - PubMed
    1. Xia Y, Wu Q, Wang H, et al. Global, regional and national burden of gout, 1990-2017: a systematic analysis of the Global Burden of Disease Study. Rheumatology (Oxford) 2020;59(7):1529–38. doi: 10.1093/rheumatology/kez476 [published Online First: 2019/10/19] - DOI - PubMed
    1. Safiri S, Kolahi AA, Cross M, et al. Prevalence, Incidence, and Years Lived With Disability Due to Gout and Its Attributable Risk Factors for 195 Countries and Territories 1990-2017: A Systematic Analysis of the Global Burden of Disease Study 2017. Arthritis & rheumatology 2020. doi: 10.1002/art.41404 [published Online First: 2020/08/06] - DOI - PubMed
    1. Te Kampe R, Janssen M, van Durme C, et al. Sex Differences in the Clinical Profile Among Patients With Gout: Cross-sectional Analyses of an Observational Study. J Rheumatol 2021;48(2):286–92. doi: 10.3899/jrheum.200113 [published Online First: 2020/07/03] - DOI - PubMed
    1. Harrold LR, Yood RA, Mikuls TR, et al. Sex differences in gout epidemiology: evaluation and treatment. Ann Rheum Dis 2006;65(10):1368–72. doi: 10.1136/ard.2006.051649 [published Online First: 2006/04/29] - DOI - PMC - PubMed

Publication types