Cross-sectional Study and Mendelian Randomization Analysis of Diet in Six Prevalent Autoimmune Diseases

Antonio Julià¹, Sergio H Martinez ², Jesús Tornero ³, Juan Cañete ⁴, Antonio Fernández-Nebro ⁵, Francisco J. Blanco ⁶, Jesús Rodríguez ⁷, Francisco Javier Lopez-Longo ⁸, Benjamín Fernandez-Gutierrez ⁹, Jordi Gratacós ¹⁰, Jose J Pérez Venegas ¹¹, Carolina Pérez ¹², Ruben Queiró ¹³, Alejandro Olivé-Marqués ¹⁴, Mercedes Alperi-López ¹⁵, Carlos Montilla ¹⁶, José Luís Andreu ¹⁷, Juan Carlos Torre-Alonso ¹⁸, Mª Ángeles Aguirre-Zamorano ¹⁹, Hèctor Corominas ²⁰, Paloma Vela ²¹, Víctor Martínez-Taboada ²², Sara Marique ²³, Joan M Nolla ²⁴, Isidoro Gonzalez ²⁵, Santiago Muñoz-Fernandez ²⁶, José Luís Marenco de la Fuente ²⁷, Carlos González ²⁸, Antonio Zea ²⁹, Maria Lopez Lasanta ³⁰, Daniel Roig ³¹, Jose Maria Pego-Reigosa ³², Mireia Lopez Corbeto ³³, Pedro Zarco ³⁴, Mercedes Freire González ³⁵, Alba Erra ³⁶, Elvira Díez ³⁷, Santos Castañeda ³⁸, Esther Rodriguez ³⁹, Alicia García ⁴⁰, Patricia Carreira ³⁹, Georgina Salvador ⁴¹, Ricardo Blanco ⁴², Cesar Diaz-Torne ⁴³, Alfredo Willisch Domínguez ⁴⁴, Joan Antonio Mosquera ⁴⁵, Simón Sánchez-Fernández ⁴⁶, Júlio Ramírez ⁴⁷ and Sara Marsal ⁴⁸, ¹Rheumatology Research Group, Vall d’Hebron Hospital Research Institute, Barcelona, Spain., Barcelona, Catalonia, Spain, ²Hospital Vall d'Hebron, Barcelona, Barcelona, Spain, ³Hospital Universitario Guadalajara, Guadalajara, Spain., Guadalajara, Castilla-La Mancha, Spain, ⁴Rheumatology Department, Hospital Clínic and IDIBAPS,, Barcelona, Spain, ⁵Hospital Carlos Haya, Malaga, Spain, ⁶Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC). As Xubias, 15006. A Coruña, España, A Coruña, Spain, ⁷Hospital Universitario de Bellvitge, Hospitalet, Spain, ⁸Hospital Universitario Gregorio Marañón, Madrid, Madrid, Spain, ⁹Hospital Clínico San Carlos, Madrid, Madrid, Spain, ¹⁰Hospital Parc Taulí, Sabadell, Catalonia, Spain, ¹¹Hospital Jerez de la Frontera, Jerez de la Frontera, Spain, ¹²Parc de Salut Mar, Barcelona, Barcelona, Spain, ¹³Hospital Universitario Central de Asturias, Oviedo, Oviedo, Spain, ¹⁴Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain, ¹⁵Hospital Universitario Central de Asturias, Oviedo, Spain, ¹⁶Hospital Clínico Universitario de Salamanca, Salamanca, Spain, ¹⁷Hospital Puerta de Hierro, Madrid, Madrid, Spain, ¹⁸Hospital Monte Naranco, Oviedo, Spain, ¹⁹IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain, ²⁰Hospital de la Santa Creu i Sant Pau, Barcelona, Barcelona, Spain, ²¹Hospital General Universitario de Alicante, Alicante, Spain, ²²Hospital Universitario Marqués de Valdecilla, Santander, Spain, ²³Hospital Regional Univeristario de Málaga, Málaga, Spain, ²⁴Hospital Universitari de Bellvitge, Hospitalet, Spain, ²⁵Hospital Universitario La Princesa, Madrid, Spain, ²⁶Hospital Universitario Infanta Sofía, Madrid, Madrid, Spain, ²⁷Hospital Valme, Sevilla, Sevilla, Spain, ²⁸Hospital Universitario Gregorio Marañón, Madrid, Spain, ²⁹Hospital Universitario Ramón y Cajal, Madrid, Madrid, Spain, ³⁰Hospital Universitari Vall Hebrón, Barcelona, Barcelona, Catalonia, Spain, ³¹Hospital Moisès Broggi, Barcelona, Sant Joan Despí, Barcelona, Singapore, ³²Complexo Hospitalario Universitario, Vigo, Spain, ³³Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain, ³⁴Hospital Universitario Fundación Alcorcón, Madrid, Madrid, Spain, ³⁵Hospital Universitario Juan Canalejo, La Coruña, Spain, ³⁶H Sant Rafael, Barcelona, Barcelona, Spain, ³⁷Complejo Asistencial Universitario de León, León, Castilla y Leon, Spain, ³⁸Rheumatology, Hospital Universitario La Princesa, Madrid, Madrid, Spain, ³⁹Hospital Universitario 12 de Octubre, Madrid, Spain, ⁴⁰Centro de Salud Virgen de los Reyes, Sevilla, Sevilla, Spain, ⁴¹Hospital Mútua Terrassa, Terrassa, Spain, ⁴²Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain, ⁴³Hospital de la Santa Creu i Sant Pau, barcelona, Catalonia, Spain, ⁴⁴Complexo Hospitalario de Ourense, Ourense, Spain, ⁴⁵Complejo Hospitalario Hospital Provincial de Pontevedra, Pontevedra, Spain, ⁴⁶Hospital La Mancha Centro, Alcázar de San Juan, Alcázar de San Juan, Spain, ⁴⁷Hospital Clínic de Barcelona, Barcelona, Spain, ⁴⁸Vall d’Hebron Hospital, Barcelona, Catalonia, Spain

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: autoimmune diseases, modifiable risk and environmental factors, nutrition

Session Information

Date: Tuesday, November 12, 2019

Title: Epidemiology & Public Health Poster III: OA, Gout, & Other Diseases

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Autoimmune diseases (AD) are complex diseases associated with both genetic and environmental risk factors. In the last 10 years major advances have been made in the characterization of the genetic basis of AD. To date, very little is known on the environmental factors associated to AD.
The objective of the present study was to characterize the dietary patterns of six of the most prevalent ADs, and evaluate the effect of disease on the observed changes.

Methods: A total cross-sectional cohort of 11,621 individuals from Spain encompassing six prevalent ADs (RA n=1,949; psoriasis (PS) n=2,186; PsA n=1,437; SLE n=699, ulcerative colitis (UC) n=1,415; Crohn’s disease (CD) n=1,952) and healthy controls (n=1,983), was recruited through the IMID-Consortium from 2,007 to 2,012. Dietary habits were registered through a common epidemiological questionnaire, including biometric, socio-demographic and lifestyle information. For each individual, the weekly consumption frequency of 13 main food categories was recorded. Disease-specific main effects and moderation by disease activity were tested for statistical significance. Multivariate linear models were used to test for association with adjustment for main confounding covariates (e.g. age, gender, geographic region, BMI). In a subset of patients and controls with GWAS data (n=7,402) mendelian randomization (MR) was used to support the causality of disease on the observed diet variation.

Results: As expected, patients with ADs targeting the digestive system -UC and CD- showed the largest food consumption differences in comparison to healthy controls. This included a highly significant increase in bread, pasta and sweets (P< 1e-8 in CD, P< 1e-5 in UC). Like IBDs, SLE and PsA patients had a higher ingestion of sweets, and RA patients showed a higher consumption of bread (P< 0.05). Specifically, chronic arthritis RA and PsA had a reduced consumption of meat (P< 5e-4) compared to controls. RA and UC (but not CD) incorporated more fruit in their diet. Testing for association between disease activity in the three rheumatic diseases -SLEDAI for SLE and DAS28 for RA and PsA- did not support a direct association between the previous food groups with severity but revealed a positive association between dairy and disease activity in RA. Using a MR approach, we provide evidence that several of the observed dietary changes are caused by the disease. High smoking cessation rates were observed in UC, CD and SLE, but not in Ps, RA and PsA. Alcohol consumption was significantly lower in all ADs compared to healthy subjects. MR analysis showed that disease was the main cause for this change of habit in SLE (P< 5e-11) and RA (P< 5e-7), but not in PsA (P=0.21).

Conclusion: Using a large cross-sectional cohort of patients and controls from the Spanish population we provide, for the first time, a simultaneous analysis of the dietary habits of six autoimmune diseases. Our results confirm the high impact of IBD on diet alteration but also show multiple previously unreported associations with food categories and rheumatic ADs. Mendelian Randomization analyses support the causal effect of disease on multiple of the observed dietary changes but also suggest the presence of reverse causation.

Disclosure: A. Julià, None; S. Martinez, None; J. Tornero, None; J. Cañete, None; A. Fernández-Nebro, None; F. Blanco, None; J. Rodríguez, None; F. Lopez-Longo, None; B. Fernandez-Gutierrez, None; J. Gratacós, None; J. Pérez Venegas, None; C. Pérez, None; R. Queiró, None; A. Olivé-Marqués, None; M. Alperi-López, None; C. Montilla, None; J. Andreu, None; J. Torre-Alonso, None; M. Aguirre-Zamorano, None; H. Corominas, None; P. Vela, None; V. Martínez-Taboada, None; S. Marique, None; J. Nolla, None; I. Gonzalez, None; S. Muñoz-Fernandez, None; J. Marenco de la Fuente, None; C. González, None; A. Zea, None; M. Lopez Lasanta, None; D. Roig, None; J. Pego-Reigosa, None; M. Lopez Corbeto, None; P. Zarco, None; M. Freire González, None; A. Erra, None; E. Díez, None; S. Castañeda, None; E. Rodriguez, None; A. García, None; P. Carreira, None; G. Salvador, None; R. Blanco, None; C. Diaz-Torne, None; A. Willisch Domínguez, None; J. Mosquera, None; S. Sánchez-Fernández, None; J. Ramírez, None; S. Marsal, Vorso Corp, 5.

To cite this abstract in AMA style:

Julià A, Martinez S, Tornero J, Cañete J, Fernández-Nebro A, Blanco F, Rodríguez J, Lopez-Longo F, Fernandez-Gutierrez B, Gratacós J, Pérez Venegas J, Pérez C, Queiró R, Olivé-Marqués A, Alperi-López M, Montilla C, Andreu J, Torre-Alonso J, Aguirre-Zamorano M, Corominas H, Vela P, Martínez-Taboada V, Marique S, Nolla J, Gonzalez I, Muñoz-Fernandez S, Marenco de la Fuente J, González C, Zea A, Lopez Lasanta M, Roig D, Pego-Reigosa J, Lopez Corbeto M, Zarco P, Freire González M, Erra A, Díez E, Castañeda S, Rodriguez E, García A, Carreira P, Salvador G, Blanco R, Diaz-Torne C, Willisch Domínguez A, Mosquera J, Sánchez-Fernández S, Ramírez J, Marsal S. Cross-sectional Study and Mendelian Randomization Analysis of Diet in Six Prevalent Autoimmune Diseases [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/cross-sectional-study-and-mendelian-randomization-analysis-of-diet-in-six-prevalent-autoimmune-diseases/. Accessed .

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