Author
MERINO, JORDI - Massachusetts General Hospital | |
GAUSCH-FERRE, MARTA - Harvard School Of Public Health | |
ELLERVIK, CHRISTINA - Boston Children'S Hospital | |
DASHTI, HASSAN - Massachusetts General Hospital | |
SHARP, STEPHEN - University Of Cambridge | |
WU, PEITAO - Boston University School Of Public Health | |
OVERVAD, KIM - Aarhus University | |
SARNOWSKI, CHLOE - Boston University School Of Public Health | |
KUOKKANEN, MIKKO - National Institute For Health And Welfare (HELSINKI) | |
LEMAITRE, ROZENN - University Of Washington | |
JUSTICE, ANNE - University Of North Carolina | |
ERICSON, ULRIKA - Lund University | |
BRAUN, KIM - Erasmus Medical Center | |
MAHENDRAN, YUVARAJ - University Of Copenhagen | |
FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC) | |
SUN, DIANJIANYI - Tulane School Of Public Health | |
CHU, AUDREY - Brigham & Women'S Hospital | |
TANAKA, TOSHIKO - National Institute On Aging (NIA, NIH) | |
LUAN, JIAN'AN - University Of Cambridge | |
HONG, JAEYOUNG - Boston University School Of Public Health | |
TJONNELAND, ANNE - Danish Cancer Society Research Center | |
DING, MING - Harvard School Of Public Health | |
LUNDQVIST, ANNAMARI - National Institute For Health And Welfare (HELSINKI) | |
MULAMAL, KENNETH - Beth Israel Deaconess Medical Center | |
ROHDE, REBECCA - University Of North Carolina | |
SCHULZ, CHRISTINA - Lund University | |
FRANCO, OSCAR - Erasmus Medical Center | |
GRARUP, NIELS - University Of Copenhagen | |
CHEN, YII - Harbor-Ucla Medical Center | |
BAZZANO, LYDIA - Tulane School Of Public Health | |
FRANKS, PAUL - Harvard School Of Public Health | |
BURING, JULIE - Brigham & Women'S Hospital | |
LANGENBERG, CLAUDIA - University Of Cambridge | |
LIU, CHING - Boston University School Of Public Health | |
HANSEN, TORBEN - University Of Copenhagen | |
JENSEN, MAJKEN - Harvard School Of Public Health | |
SAAKSJARVI, KATRI - National Institute For Health And Welfare (HELSINKI) | |
PSATY, BRUCE - University Of Washington | |
YOUNG, KRISTIN - University Of North Carolina | |
HINDY, GEORGE - Massachusetts General Hospital | |
SANDHOLT, CAMILLA - University Of Copenhagen | |
RIDKER, PAUL - Brigham & Women'S Hospital | |
ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
MEIGS, JAMES - Massachusetts General Hospital | |
PEDERSON, OLUF - University Of Copenhagen | |
KRAFT, PETER - Harvard School Of Public Health | |
PEROLA, MARKUS - National Institute For Health And Welfare (HELSINKI) | |
NORTH, KARI - University Of North Carolina | |
ORHO-MELANDER, MARJU - Lund University | |
VOORTMAN, TRUDY - Erasmus Medical Center | |
TOFT, ULLA - Copenhagen University | |
ROTTER, JEROME - Harbor-Ucla Medical Center | |
QI, LU - Harvard School Of Public Health | |
FOROUHI, NITA - University Of Cambridge | |
MOZAFFARIAN, DARIUSH - Friedman School At Tufts | |
SORENSEN, THORKILD - University Of Copenhagen | |
STAMPFER, MEIR - Harvard School Of Public Health | |
MANNISTO, SATU - National Institute For Health And Welfare (HELSINKI) | |
SELVIN, ELIZABETH - Johns Hopkins School Of Public Health | |
IMAMURA, FUMIAKI - University Of Cambridge | |
SALOMAA, VEIKKO - National Institute For Health And Welfare (HELSINKI) | |
HU, FRANK - Harvard School Of Public Health | |
WAREHAM, NICK - Boston University School Of Public Health | |
DUPUIS, JOSEE - Boston University School Of Public Health | |
SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
KILPELAINEN, TUOMAS - University Of Copenhagen | |
CHASMAN, DANIEL - Broad Institute Of Mit/harvard | |
FLOREZ, JOSE - Massachusetts General Hospital |
Submitted to: The BMJ
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 6/10/2019 Publication Date: 7/25/2019 Citation: Merino, J., Gausch-Ferre, M., Ellervik, C., Dashti, H.S., Sharp, S.J., Wu, P., Overvad, K., Sarnowski, C., Kuokkanen, M., Lemaitre, R.N., Justice, A.E., Ericson, U., Braun, K.V., Mahendran, Y., Frazier-Wood, A.C., Sun, D., Chu, A.Y., Tanaka, T., Luan, J., Hong, J., Tjonneland, A., Ding, M., Lundqvist, A., Mulamal, K., Rohde, R., Schulz, C.A., Franco, O.H., Grarup, N., Chen, Y.D., Bazzano, L., Franks, P.W., Buring, J.E., Langenberg, C., Liu, C.T., Hansen, T., Jensen, M.K., Saaksjarvi, K., Psaty, B.M., Young, K.L., Hindy, G., Sandholt, C.H., Ridker, P.M., Ordovas, J.M., Meigs, J.B., Pederson, O., Kraft, P., Perola, M., North, K.E., Orho-Melander, M., Voortman, T., Toft, U., Rotter, J.I., Qi, L., Forouhi, N.G., Mozaffarian, D., Sorensen, T.1., Stampfer, M.J., Mannisto, S., Selvin, E., Imamura, F., Salomaa, V., Hu, F.B., Wareham, N.J., Dupuis, J., Smith, C.E., Kilpelainen, T.O., Chasman, D.I., Florez, J.C. 2019. Quality of dietary fat and genetic risk of type 2 diabetes: Individual participant data meta-analysis. The BMJ. 366:14292. https://doi.org/10.1136/bmj.l4292. DOI: https://doi.org/10.1136/bmj.l4292 Interpretive Summary: Too much fat in the diet, especially saturated fat, increases the risk of type 2 diabetes. We know that the extent to which dietary fat increases the risk of type 2 diabetes is different between different people, but we don't know why. This makes it hard to focus our dietary interventions for preventing type 2 diabetes on those most at risk, and hard to tailor our advice for preventing type 2 diabetes to individual needs. To better understand who is most at risk of type 2 diabetes from the fat in their diet, we examined whether having genes that predispose you to developing type 2 diabetes regardless of your dietary intake, also alter your responses to dietary fat intake and so increase your risk. Using data from over 100,000 participants across the world, we found that this was not the case: whether consuming dietary fat increases your risk for type 2 diabetes is not dependent on your background genetic risk for this condition. This information is useful mostly to researchers – either those who are trying to identify why certain genetic risk factors increase your risk of type 2 diabetes, or those who are trying to identify why some people develop type 2 diabetes as a result of a high-fat diet, but others do not. Technical Abstract: Our objective was to investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes using individual participant data meta-analysis. Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators. Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score. Of 102,305 participants from 15 prospective cohort studies, 20,015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I**2=7.1%, t**2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I**2=18.0%, t**2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, t**2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I**2=25.9%, t**2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed. These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk. |