Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts

Authors: MOZAFFARIAN, DARIUSH - Tufts University; DASHTI, HASSAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WOJCZYNSKI, MARY - Washington University; CHU, AUDREY - Brigham & Women'S Hospital; NETTLETON, JENNIFER - University Of Texas; MANNISTO, SATU - National Institute For Health And Welfare (HELSINKI); KRISTIANSSON, KATI - National Institute For Health And Welfare (HELSINKI); REEDIK, MAGI - University Of Tartu; LAHTI, JARI - University Of Helsinki; HOUSTON, DENISE - Wake Forest University; CORNELIS, MARILYN - Harvard University; VAN ROOIJ, FRANK - Erasmus Medical Center; DIMITRIOU, MARIA - Harokopio University Of Athens; KANONI, STAVROULA - Queen Mary University Of London; MIKKILA, VERA - University Of Helsinki; STEFFEN, LYN - University Of Minnesota; DE OLIVEIRA OTTO, MARCIA - University Of Texas; QI, LU - Netherlands Genomics Initiative; PSATY, BRUCE - University Of Washington; DJOUSSE, LUC - Harvard University; ROTTER, JEROME - Harbor-Ucla Medical Center; HARALD, KENNET - National Institute For Health And Welfare (HELSINKI); PEROLA, MARKUS - National Institute For Health And Welfare (HELSINKI); RISSANEN, HARRI - National Institute For Health And Welfare (HELSINKI); JULA, ANTTI - National Institute For Health And Welfare (HELSINKI); FISCHER, KRISTA - University Of Tartu; MIHAILOV, EVELIN - University Of Tartu; FEITOSA, MARY - Washington University; NGWA, JULIUS - Boston University; XUE, LUTING - Boston University; JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PERALA, MIA-MARIA - National Institute For Health And Welfare (HELSINKI); PALOTIE, AARNO - University Of Helsinki; LIU, YONGMEI - Wake Forest University; NALLS, MIKE - National Institute On Aging (NIA, NIH); FERRRUCCI, LUIGI - National Institute On Aging (NIA, NIH); HERNANDEZ, DENA - National Institute On Aging (NIA, NIH); MANICHAIKUL, ANI - University Of Virginia; TSAI, MICHAEL - University Of Minnesota; KIEFTE-DE JONG, JESSICA - Erasmus Medical Center; HOFMAN, ALBERT - Erasmus Medical Center; UITTERLINDEN, ANDRE - Erasmus Medical Center; RALLIDIS, LOUKIANOS - 32892; RIDKER, PAUL - Harvard University; ROSE, LYNDA - Brigham & Women'S Hospital; BURING, JULIE - Harvard University; LEHTIMAKI, TERHO - University Of Tampere; KAHONEN, MIKA - University Of Tampere; VIIKARI, JORMA - University Of Turku; LEMAITRE, ROZENN - University Of Washington; SALOMAA, VEIKKO - National Institute For Health And Welfare (HELSINKI); KNEKT, PAUL - National Institute For Health And Welfare (HELSINKI); METSPALU, ANDRES - University Of Tartu; BORECKI, INGRID - Washington University; CUPPLES, L. ADRIENNE - Boston University; ERIKSSON, JOHAN - National Institute For Health And Welfare (HELSINKI); KRITCHEVSKY, STEPHEN - Wake Forest University; BANDINELLI, STEFANIA - Azienda Sanitaria Di Firenze; SISCOVICK, DAVID - New York Academy Of Medicine; FRANCO, OSCAR - Erasmus Medical Center; DELOUKAS, PANOS - University Of London; DEDOUSSIS, GEORGE - Harokopio University Of Athens; CHASMAN, DANIEL - Harvard University; RAITAKARI, OLLI - University Of Turku; TOSHIKO, TANAKA - National Institute On Aging (NIA, NIH)

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2017
Publication Date: 12/13/2017
Citation: Mozaffarian, D., Dashti, H.S., Wojczynski, M.K., Chu, A.Y., Nettleton, J.A., Mannisto, S., Kristiansson, K., Reedik, M., Lahti, J., Houston, D.K., Cornelis, M.C., Van Rooij, F.J., Dimitriou, M., Kanoni, S., Mikkila, V., Steffen, L.M., De Oliveira Otto, M.C., Qi, L., Psaty, B., Djousse, L., Rotter, J.I., Harald, K., Perola, M., Rissanen, H., Jula, A., Fischer, K., Mihailov, E., Feitosa, M.F., Ngwa, J.S., Xue, L., Jacques, P.F., Perala, M., Palotie, A., Liu, Y., Nalls, M.A., Ferrrucci, L., Hernandez, D., Manichaikul, A., Tsai, M.Y., Kiefte-De Jong, J.C., Hofman, A., Uitterlinden, A.G., Rallidis, L., Ridker, P.M., Rose, L.M., Buring, J., Lehtimaki, T., Kahonen, M., Viikari, J., Lemaitre, R., Salomaa, V., Knekt, P., Metspalu, A., Borecki, I.B., Cupples, L., Eriksson, J.G., Kritchevsky, S.B., Bandinelli, S., Siscovick, D., Franco, O.H., Deloukas, P., Dedoussis, G., Chasman, D.I., Raitakari, O., Toshiko, T. 2017. Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts. PLoS One. 12(12):e0186456. https://doi.org/10.1371/journal.pone.0186456.
DOI: https://doi.org/10.1371/journal.pone.0186456

Interpretive Summary: Research has shown that consumption of fish and long-chain omega-3 fatty acids (found in fish) is linked to lower risk of several chronic diseases, including fatal coronary heart disease. Despite the well-established health benefits of fish, in Western nations approximately 2/3 of the population consume no or little fish. "Personalized nutrition" is the notion that a person's genes can influence their behaviors and responses to the environment. Understanding how specific genes may alter fish and long-chain omega-3 fatty acid consumption may have implications for understanding influences on variation in fish intake within populations and the biology behind why individuals may be partial to eating fish or not. The objective of this study was to identify common genetic variants that influence fish and long-chain omega-3 fatty acid intake. In particular, we focused on dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA). In this study, we combined data from 17 cohort studies to conduct a genome-wide association study (GWA). Our results showed that genetic variation did not have a large effect on fish consumption. Thus, it is likely that other modifiable factors, such as childhood diet, culture, education, income, and food availability, are the main determinants of differences in fish consumption across populations. In order to increase fish consumption, non-genetic factors should be focused on.

Technical Abstract: Background: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design: We conducted genome-wide association (GWA) meta-analysis of fish (n=86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10^-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10^-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. Conclusions: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.