Interactions Between Genetic Risk and Diet Influencing Risk of Incident Female Gout: Discovery and Replication Analysis of Four Prospective Cohorts
Objective To examine whether the cross‐sectional gene–diet interaction for prevalent hyperuricemia among women translates prospectively to risk of incident female gout. Methods We analyzed the interaction between genetic predisposition and adherence to a healthy dietary pattern (i.e., Dietary Approa...
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| Published in: | Arthritis & rheumatology (Hoboken, N.J.) Vol. 75; no. 6; pp. 1028 - 1038 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Boston, USA
Wiley Periodicals, Inc
01.06.2023
Wiley Subscription Services, Inc |
| Subjects: | |
| ISSN: | 2326-5191, 2326-5205, 2326-5205 |
| Online Access: | Get full text |
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| Summary: | Objective
To examine whether the cross‐sectional gene–diet interaction for prevalent hyperuricemia among women translates prospectively to risk of incident female gout.
Methods
We analyzed the interaction between genetic predisposition and adherence to a healthy dietary pattern (i.e., Dietary Approaches to Stop Hypertension [DASH] score) on risk of incident female gout in 18,244 women from Nurses’ Health Study (NHS; discovery) and 136,786 women from 3 additional prospective female cohorts from the US and UK (replication). Genetic risk score (GRS) was calculated from 114 urate‐associated loci.
Results
In the NHS and replication cohorts, association between diet and gout risk was larger and stronger among women with higher genetic risk. In all cohorts combined, compared to women with an unhealthy DASH score (less than the mean score), multivariable relative risk (RR) for incident gout among women with a healthy DASH score (greater than/equal to the mean score) was 0.67 (95% confidence interval [95% CI] 0.60–0.76) among higher GRS (greater than/equal to the mean score) and 0.91 (0.78–1.05) among lower GRS (P for multiplicative interaction = 0.001); multivariable RR for higher versus lower GRS was 2.03 (95% CI 1.80–2.29) and 1.50 (95% CI 1.31–1.71) among unhealthy and healthy DASH score groups, respectively. Additive interaction was also significant, in both the discovery and replication cohorts (P < 0.001), with 51% of the excess risk attributable to the additive gene–diet interaction in all cohorts combined.
Conclusion
The deleterious effect of genetic predisposition on risk of incident female gout was more pronounced among women with unhealthy diets, with nearly half the excess risk attributable to this gene–diet interaction. These data elucidate the important synergy of genetics and diet for female gout development. |
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| Bibliography: | https://onlinelibrary.wiley.com/doi/10.1002/art.42419 Author disclosures and a graphical abstract can be found online at Supported by the NIH (grants P50‐AR‐060772, R01‐AR‐065944, R01‐AR‐056291, UM1‐CA‐186107, R01‐CA‐49449, U01‐CA‐176726, and R01‐CA‐67262). The Women's Genome Health Study is supported by the National Heart, Lung, and Blood Institute (grants HL043851 and HL0804670) and the National Cancer Institute (awards CA047988 and UM1 CA182913), with additional support for genotyping provided by Amgen. Dr. McCormick's work was supported by the NIH (award K99‐AR‐080243). Dr. Curhan's work was supported by the NIH (grant K24‐DK‐091417). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. . ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ISSN: | 2326-5191 2326-5205 2326-5205 |
| DOI: | 10.1002/art.42419 |