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.
- crystal arthropathies
Data availability statement
All data relevant to the study are included in the article. No additional data available.
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Handling editor Josef S Smolen
NM and CY contributed equally.
Contributors CY and HC designed this study. HC and GC collected the data. NL, ADJ and HC provided statistical expertise. NM, CY, NL, ADJ and HC analysed the data. CY wrote the first draft of the manuscript. All authors interpreted the results and approved the final version of the manuscript. HC is the guarantor.
Funding This study was supported by the National Institutes of Health (P50 AR060772, R01 AR065944, R01 AR056291, U01 CA167552, UM1 CA186107 and U01 CA176726). NM was supported by a Fellowship Award from the Canadian Institutes of Health Research. CY was supported by the National Institutes of Health Ruth L Kirschstein Institutional National Research Service Award (T32 AR007258) and the Rheumatology Research Foundation Scientist Development Award. GC is supported by the National Institutes of Health (K24 DK091417).
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.
Provenance and peer review Not commissioned; externally peer reviewed.
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