Research Project: Genomics, Nutrition, and Health

Location: Jean Mayer Human Nutrition Research Center On Aging

2017 Annual Report

Objectives
1: Identify metabolomic-based biomarkers of dietary and exercise behavior in normal-weight and obese elderly individuals and the genetic variants associating with the baseline levels of these metabolites. 1.A. Identify metabolomic-based biomarkers of dietary behavior in normal-weight and obese aging individuals and the genetic variants associating with endogenous variability of these metabolites. 1.B. Identify metabolomic-based biomarkers of physical activity in normal-weight and obese aging individuals and the genetic variants associating with endogenous variability of these metabolites. 2: Determine the demographic, behavioral, metabolomic and genetic drivers of the excess obesity in elderly population(s) suffering health disparity. 3: Determine the relationships between aging-related changes in gene expression, endogenous and exogenous microRNAs, metabolic factors and chronotype in response to metabolic challenges such as unhealthy dietary habits, high-fat loads and physical inactivity. 4: Identify genomic, and epigenomic and metabolic markers that predict cardiovascular status and metabolic health during aging and define specific dietary, physical activity and other lifestyle factors that are most suitable to an individual’s genetic and epigenetic profile. 5: Use a multi-omics approach to identify multi-level genome/metagenome/diet interactions that modulate inflammation and aging pathways in normal-weight and obese individuals. 5.A. Determine which of a panel of aging and obesity-related phenotypes associate with genetic markers of obesity in an obese-non-obese comparison (or, in a manner dependent on obesity status) and which of those genetic associations are modulated by dietary factors and exercise. 5.B. Assess microRNA expression levels as correlating with the obese condition irrespective of genetics. 5.C. Collect metabolomics data to define individuals metabolically as obese or non-obese, irrespective of anthropometrics. 5.D. Perform gene network, systems biology analysis on those genes and genetic markers showing associations, either modified by diet or exercise or not, with the aging and obesity-related phenotypes.

Approach
Our research on the genetic basis of the responses to diet and their metabolic consequences has demonstrated that the onset and progression of age-related disorders depends on an individual’s metabolic flexibility. With respect to cardiometabolic diseases several factors act in concert and converge to challenge metabolic flexibility. These include an inadequate diet, insufficient physical activity, chronodisruption, decreased metabolic reserve, altered gut microbiome, and reduced immune system capacity. Our primary focus is to determine the specific elements from each of these factors that interact together and with common genetic variants to either promote or disrupt a program of metabolic flexibility in the context of aging, obesity and cardiovascular disease. Our approach aims to identify new metabolite-based markers, substantiate intake of certain foods, nutrients or dietary patterns, define the degree and mechanisms by which circadian control affects cardiometabolic diseases, to describe the roles of microRNAs in these diseases, and to do so in the context of populations suffering health disparities. This will be tested, using high throughput “omic” (i.e., genomics, epigenomics, metabolomics) techniques, both in ongoing studies of free-living populations from different ethnic groups and in intervention studies. We also propose to establish statistical methods whereby a genome-optimized diet is evaluated for its ability to lower plasma triglycerides. Lastly, available datasets will be used to construct gene-SNP-metabolite-diet-aging networks for the purpose of generating testable hypotheses relevant to delaying the onset and progression of cardiometabolic disorders. Outcomes of this research will generate new and better strategies for the prevention of age-related disorders and for slowing the aging process using nutritional and behavioral approaches.

Progress Report
Within the reporting period the project Genomics, Nutrition and Health has had significant progress. Of note are the advances made in the integration of high throughput molecular techniques, commonly known as OMICS. Along these lines, we completed methylome (the set of nucleic acid methylation modifications in an organism's genome or in a particular cell), transcriptome (the complete set of RNA molecules (transcripts) produced in a cell or a population of cells) and metabolome (the complete set of metabolites found in a biological sample) profiling in four groups of participants with different genotypes at the APOA2-265 C/T polymorphism (CC versus TT) consuming either a low or high saturated fat (SFA) diet. These subjects were all of Puerto Rican origin and live in the Boston area. From our methylome analysis, we identified a methylation site known as cg04436964 near the upstream region of APOA2 that exhibited significant genotype- and dietary saturated fat- related differences in the level of methylation. These findings may represent the molecular basis for a highly significant APOA2, saturated fat, and obesity interaction that was previously reported by our group. This finding was validated in two additional populations: 107 participants with CC and 272 with TT genotype from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study and 170 participants with CC genotype and 73 with TT genotype from the Framingham Heart Study (FHS). In addition, we showed that the methylation level at cg04436964 was negatively correlated with APOA2 expression in whole blood. Furthermore, we found that participants with the CC genotype exhibited low expression of APOA2 compared to the TT genotype with high SFA intake, but expression did not differ by genotype at low SFA intake. This further exemplifies a more mechanistic basis for the above-mentioned APOA2, saturated fat, and obesity interaction. Moreover, integration of these findings with the metabolomics data supported the notion that these alterations may be associated with tryptophan metabolism. Tryptophan is a precursor to the neurotransmitter serotonin involved in appetite. Therefore, this integrative OMICS work provides some important clues to identify the mechanisms for a well-proven and highly relevant gene diet interaction involving the APOA2 gene, dietary intake of saturated fat, and obesity and provides solid footing to move forward in the field of personalized nutrition. This progress relates to sub-objectives 1A, 5A, 5C, and 5D and objectives 2 and 4. Continuing the theme of OMIC integration and in collaboration with Tennessee State University (agreement 8050-51000-098-04S), we completed metabolome profiling using serum and transcriptome profiling using liver and skeletal muscle in three groups of aged mice with different lifespans after intervention with dietary epicatechin (from cacao). Over 390 metabolites were identified between three groups: old mice control, epicatechin-treated old mice, and young mice. Principal component analysis indicated that epicatechin reversed the metabolome patterns characterized by 30 metabolites in old mice to the patterns observed in of young mice. One potential aging-associated pathway, nicotinate and nicotinamide metabolism, was identified and significantly enriched. From transcriptome analysis, 204 genes displayed differential expression between control- and epicatechin-treated old mice. Over 29 pathways related to skeletal muscle were identified. Expressions in a set of genes were significantly reversed in the skeletal muscle of epicatechin-treated old mice compared to that of young mice. Some of the differential expression genes were further confirmed with protein expression in skeletal muscle. A manuscript is being prepared for publication, and an invention disclosure on epicatechin for prevention of muscle aging is being prepared for submission. This progress relates to objectives 3 and 4.

Accomplishments
1. Eating lunch late may slow weight loss. To maintain a healthy weight and active lifestyle, people have focused on what they eat and how they exercise but have not considered whether the timing of these activities mattered. ARS and ARS-funded researchers in Boston, Massachusetts discovered that eating lunch late slows mobilization of fat and can affect successful weight loss in individuals with certain genotypes. In collaboration with Spanish investigators they studied the effect of certain genetic variants and lunch timing on weight loss in the ONTIME (Obesity, Nutrigenetics, Timing, Mediterranean) Study. These findings add a new dimension to predicting weight loss success and may lead to more precise and personalized treatment of obesity.

Review Publications
Lai, C., Ma, Y., Parnell, L.D. 2016. Genetics and gene-environment interactions on longevity and lifespan. In: Qi, L., Editor. Gene-Environment Interactions and Human Diseases. Hauppauge, NY: Nova Science Publishers, Inc. p. 245-264.
Gomez-Delgado, F., Delgado-Lista, J., Lopez-Moreno, J., Rangel-Zuñiga, O., Alcala-Diaz, J., Leon Acuña, A., Baba, A.C., Yubero-Serrano, E., Torres Peña, J., Camargo, A., Garcia-Rios, A., Cabellero, J., Castaño, J., Ordovas, J.M., Lopez-Miranda, J., Perez-Martinez, P. 2016. Telomerase RNA Component (TERC) genetic variants interact with the mediterranean diet modifying the inflammatory status and its relationship with aging: CORDIOPREV study. Journal of Gerontology Medical Science. doi: 10.1093/gerona/glw194.
Ma, Y., Ordovas, J.M. 2016. The integration of epigenetics and genetics in nutrition research for CVD risk factors. Proceedings of the Nutrition Society. doi: 10.1017/S0029665116000823.
Yubero-Serrano, E.M., Delgado-Lista, J., Alcala-Diaz, J.F., Garcia-Rios, A., Perez-Caballero, A.I., Blanco-Rojo, R., Gomez-Delgado, F., Marin, C., Tinahones, F., Caballero, J., Ordovas, J.M., Van Ommen, B., Perez-Jimenez, F., Perez-Martinez, P., Lopez-Miranda, J. 2016. A dysregulation of glucose metabolism control is associated with carotid atherosclerosis in patients with coronary heart disease (CORDIOPREV-DIAB study). Atherosclerosis. doi: 10.1016/j.atherosclerosis.2016.07.903.
Ma, Y., Smith, C.E., Lai, C., Invin, R.M., Parnell, L.D., Lee, Y., Pham, L., Aslibekyan, S., Claas, S.A., Tsai, M.Y., Borecki, I.B., Kabagambe, E.K., Ordovas, J.M., Absher, D., Donna, A.K. 2016. Genetic variant modifies the effect of N3 PUFAs on DNA methylation of IL6 in the Genetics of Lipid Lowering Drugs and Diet Network study. Epigenetics. doi: 10.1002/mnfr.201500436.
Laclaustra, M., Hurtado-Roca, L., Sendin, M., Leon, M., Ledesma, M., Andres, E., Fernandez-Ortiz, A.I., Guallar, E., Ordovas, J.M., Casasnovas Lenguas, J. 2015. Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on spanish men. Nutrition, Metabolism and Cardiovascular Diseases. 25:1095-1103.
Mico, V., Martin, R., Lasuncion, M., Ordovas, J.M., Daimiel, L. 2016. Unsuccessful detection of plant microRNAs in beer, extra virgin olive oil and human plasma after an acute ingestion of extra virgin olive oil. Plant Foods for Human Nutrition. doi: 10.1007/s11130-016-0534-9.
Laclaustrta, M., Casasnovas, J.A., Fernandes-Ortiz, A., Fuster, V., Leon-Latre, M., Jimenez Borreguero, L.J., Pocovi, M.M., Hurtado-Roca, Y., Ordovas, J.M., Jarauta, E., Guallar, E., Ibanez, B., Civeira, F. 2016. Femoral and carotid subclinical atherosclerosis association with risk factors and coronary calcium: the AWHS study. Journal of the American College of Cardiology. doi: 10.1016/j.jacc.2015.12.056.
Gonzalea-Calvo, L., Dervishi, E., Joy, M., Sarto, P., Martin-Hernandez, R., Serrano, M., Ordovas, J.M., Calvo, J. 2017. Genome-wide expression profiling in muscle and subcutaneous fat of lambs in response to the intake of concentrate supplemented with vitamin E. BMC Genomics. doi: 10.1186/s12864-016-3405-8.
Barragan, R., Coltell, O., Asensio, E.M., Frances, F., Sorli, J.V., Estruch, R., Salas-Huetos, A., Ordovas, J.M., Corella, D. 2016. MicroRNAs and drinking: association between the pre-miR-27a rs895819 polymorphism and alcohol consumption in a Mediterranean population. International Journal of Molecular Sciences. doi: 10.3390/ijms17081338.
Love-Gregory, L., Kraja, A.T., Allum, F., Aslibekyan, S., Hedman, A.K., Duan, Y., Borecki, I.B., Arnett, D.K., Mccarthy, M.I., Deloukas, P., Ordovas, J.M., Hopkins, P.N., Grundberg, E., Abumrad, N.A. 2016. Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36. Journal of Lipid Research. doi: 10.1194/jlr.P065250.
Talavera-Garcia, E., Delgado-Lista, J., Garcia-Rios, A., Delgado-Casado, N., Gomez-Luna, P., Gomez-Garduño, A., Gomez-Delgado, F., Alcala-Diaz, J.F., Yubero-Serrano, E., Marin, C., Perez-Caballero, A.I., Fuentes-Jimenez, F.J., Camargo, A., Rodriguez-Cantalejo, F., Tinahones, F.J., Ordovas, J.M., Perez- Jimenez, F., Perez-Martinez, P., Lopez-Miranda, J. 2016. Influence of obesity and metabolic disease on carotid atherosclerosis in patients with coronary artery disease (CordioPrev study). PLoS One. doi: 10.1371/journal.pone.0157213.
Noel, S.E., Arevalo, S., Smith, C.E., Lai, C., Dawson-Hughes, B., Ordovas, J.M., Tucker, K.T. 2016. Genetic admixture and body composition in Puerto Rican adults from the Boston Puerto Rican Osteoporosis Study. Journal of Bone and Mineral Research. doi: 10.1007/s00774-016-0775-6.
Dashti, H.S., Zuurbier, L.A., De Jonge, E., Voortman, T., Jacques, P.F., Lamon-Fava, S., Scheer, F.A., Kiefte-De Jong, J.C., Hofman, A., Ordovas, J.M., Franco, O.H., Tiemeier, H. 2016. Actigraphic sleep fragmentation, efficiency and duration associate with dietary intake in the Rotterdam study. Journal of Sleep Research. doi: 10.1111/jsr.12397.
Corella, D., Asensio, E.M., Coltell, O., Sorli, J.V., Estruch, R., Martinez-Gonzalez, M., Salas-Salvadó, J., Castañer, O., Arós, F., Lapetra, J., Serra-Majem, L., Gómez-Gracia, E., Ortega-Azorín, C., Fiol, M., Espino, J.D., Díaz-López, A., Fitó, M., Ros, E., Ordovas, J.M. 2016. CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial. Cardiovascular Diabetology. 15:4. doi: 10.1186/s12933-015-0327-8.
Celis-Morales, C., Livingstone, K.M., O'Donovan, C.B., Woolhead, C., Forster, H., Walsh, M.C., Marsaux, C.F., Macready, A.L., Fallaize, R., Tsirigoti, L., Lambrinou, C.P., Efstathopoulou, E., Moschonis, G., Navas-Carretero, S., Can-Cristobal, R., Kolossa, S., Hallmann, J., Godlewska, M., Surwilla, A., Traczyk, I., Drevon, C.A., Bouwman, J., Grimaldi, K., Parnell, L.D., Manios, Y., Daniel, H., Martinez, J., Lovegrove, J.A., Gibney, E.R., Brennan, L., Saris, W.H., Gibney, M., Mathers, J.C. 2016. Effect of personalized nutrition on health-related behavior change: evidence from the Food4Me randomized controlled trial. International Journal of Epidemiology. doi: 10.1093/ije/dyw186.
Day, K., Waite, L.L., Alonso, A., Irvin, M.R., Zhi, D., Thibeault, K.S., Aslibekyan, S., Hidalgo, B., Borecki, I., Ordovas, J.M., Arnett, D.K., Tiwari, H.K., Absher, D.M. 2016. Heritable DNA methylation in CD4+ cells among complex families displays genetic and non-genetic effects. PLoS One. doi: 10.1371/journal.pone.0165488.
Ma, Y., Smith, C.E., Lai, C., Irvin, M.R., Parnell, L.D., Lee, Y., Pham, L.D., Aslibekyan, S., Claas, S.A., Tsai, M.Y., Borecki, I.B., Kagambe, E.K., Ordovas, J.M., Absher, D., Arnett, D.K. 2016. The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter. Epigenetics. 60(2):410-419. doi: 10.1002/mnfr.201500436.
Ding, M., Huang, T., Bergholdt, H.K., Frazier Wood, A.C., Aslibekyan, S., North, K.E., Voortman, T., Graff, M., Smith, C.E., Lai, C., Varbo, A., Lemaitre, R.N., De Jonge, E.A., Fumeron, F., Corella, D., Wang, C.A., Tjonneland, A., Overvad, K., Sorensen, T.I., Feitosa, M.F., Wojczynski, M.K., Kahonen, M., Ahmad, S., Trndytom, F., Psaty, B.M., Siscovick, D.S., Barroso, I., Johansson, I., Hernandez, D.G., Ferrucci, L., Bandinelli, S., Linneberg, A., Sandholt, C.H., Pedersen, O., Hansen, T., Schulz, C., Sonestedt, E., Orho-Melander, M., Chen, T., Rotter, J.I., Allison, M.A., Rich, S.S., Sorli, J.V., Coltell, O., Pennell, C.E., Eastwood, P., Hofman, A., Uitterlinden, A.G., Zillikens, M., Van Rooij, F.J., Chu, A.Y., Rose, L.M., Ridker, P.M., Viikari, J., Raitakara, O., Lehtimaki, T., Mikkila, V., Willett, W.C., Wang, Y., Tucker, K.L., Ordovas, J.M., Kilpelainen, T.O., Province, M.A., Franks, P.W., Arnett, D.K., Tanaka, T., Toft, U., Ericson, U., Franco, O.H., Mozaffarian, D., Hu, F.B., Chasman, D.I., Nordestgaard, B.G., Ellervik, C., Qi, L. 2017. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study. British Medical Journal. doi: 10.1136/bmj.j1000.
Irvin, M.R., Rotroff, D.M., Aslibekyan, S., Zhi, D., Hidalgo, B., Motsinger-Reif, A., Marvel, S., Srinivasainagendra, V., Claas, S.A., Buse, J.B., Straka, R.J., Ordovas, J.M., Borecki, I.B., Guo, X., Chen, I.Y., Rotter, J.I., Wagner, M.J., Arnett, D.K. 2016. A genome-wide study of lipid response to fenofibrate in Caucasians: a combined analysis of the GOLDN and ACCORD studies. Pharmacogenetics and Genomics. 26(7):324-333.
Ma, Y., Follis, J., Smith, C.E., Tanaka, T., Manichaikl, A., Chu, A.Y., Samieri, C., Zhou, X., Guan, W., Wang, L., Biggs, M., Chen, Y., Hernandez, D., Borecki, I.B., Chasman, D.I., Rich, S.S., Ferrucci, L., Irvin, M.R., Aslibekyan, S., Zhi, D., Tiwari, H.K., Claas, S.A., Sha, J., Kabagambe, E.K., Lai, C., Parnell, L.D., Lee, Y., Amouyel, P., Lambert, J., Psaty, B.M., King Irena, Mozaffarian, D., Mcknight, B., Bandinelli, S., Tsai, M.Y., Ridker, P.M., Ding, J., Mstat, K.L., Liu, Y., Sotoodehnia, N., Barberger-Gateau, P., Steffen, L.M., Siscovick, D.S., Absher, D.M., Arnett, D.K., Ordovas, J.M., Lemaitre, R.N. 2016. Interaction of methylation-related genetic variants with circulating fatty acids on plasma lipids: a meta-analysis of 7 studies & methylation analysis of 3 studies in the Cohorts for Heart & Aging Research. American Journal of Clinical Nutrition. doi: 10.3945/ajcn.115.112987.
Delgado-Lista, J., Perez-Martinez, P., Garcia-Rios, A., Alcala-Diaz, J.F., Perez-Caballero, A.I., Gomez-Delgado, F., Fuentes, F., Quintana-Navarro, G., Lopez-Segura, F., Ortiz-Morales, A.M., Delgado-Casado, N., Yubero-Serrano, E.M., Camargo, A., Marin, C., Rodriguez-Cantalejo, F., Gomez-Luna, P., Ordovas, J.M., Lopez-Miranda, J., Perez-Jimenez, F. 2016. Coronary diet intervention with olive oil and cardiovascular prevention study (the CORDIOPREV study); rationale, methods, and baseline characteristics: a clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients. American Heart Journal. doi: 10.1016/j.ahj.2016.04.011.
Perez-Martinez, P., Alcala-Diaz, J.F., Kabagambe, E.K., Garcia-Rios, A., Tsai, M.Y., Delgado-Lista, J., Kolobou, G., Straka, R.J., Gomez-Delgado, F., Hopkins, P.N., Marin, C., Borecki, I.B., Yubero-Serrano, E.M., Hixson, J.E., Camargo, A., Province, M.A., Lopez-Moreno, J., Rodriguez-Cantalejo, F., Tinahones, F.J., Mikhailidis, D., Perez-Jimenez, F., Arnett, D.K., Ordovas, J.M., Lopez-Miranda, J. 2016. Assessment of postprandial triglycerides in clinical practice: validation in a general population and coronary heart disease patients. Journal of Clinical Lipidology. doi: 10.1016/j.jacl.2016.05.009.
Zanoni, P., Khetarpal, S.A., Larach, D.B., Hancock-Cerutti, W.F., Millar, J.S., Cuchel, M., Derohannessian, S., Kontush, A., Surendran, P., Saleheen, D., Trompet, S., Jukema, J., De Craen, A., Deloukas, P., Sattar, N., Ford, I., Packard, C., Majumder, A., Alam, D.S., Angelantonio, E.D., Abecasis, G., Chowdhury, R., Erdmann, J., Nordestgaard, B.G., Nielsen, S.F., Tybjaerg-Hansen, A., Schmidt, R.F., Kuulasmaa, K., Liu, D., Perola, M., Blankenberg, S., Salomaa, V., Mannisto, S., Amouyel, P., Arveiler, D., Ferrieres, J., Muller-Nurasyid, M., Ferrario, M., Kee, F., Willer, C.J., Samani, N., Schunkert, H., Butterworth, A.S., Howson, J.M., Peloso, G.M., Stitziel, N.O., Danesh, J., Kathiresan, S., Rader, D.J., Ordovas, J.M. 2016. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science. doi: 10.1126/science.aad3517.
Rangel Zúñiga, O., Corina, A., Lucena-Porras, B., Cruz-Teno, C., Gómez-Delgado, F., Jiménez-Lucena, R., Alcalá Díaz, J., Haro Mariscal, C., Yubero-Serrano, E., Delgado-Lista, J., López Moreno, J., Rodriguez-Cantealejo, F., Carmargo, A., Tinahones, F., Ordovas, J.M., López Miranda, J., Pérez Martínez, P. 2016. TNFA gene variants related to the inflammatory status and its association with cellular aging: From the CORDIOPREV study. Experimental Gerontology. 83:56–62.
Bigornia, S.J., Harris, W.S., Falcon, L.M., Ordovas, J.M., Lai, C., Tucker, K.L. 2016. The omega-3 index is inversely associated with depressive symptoms among individuals with elevated oxidative stress biomarkers. Journal of Nutrition. 146(4):758-766. doi: 10.3945/jn.115.222562.
Penalvo, J.L., Fernandez-Friera, L.L., Lopez-Melgar, B., Uzhova, I., Oliva, B., Fernandez-Alvira, J.M., Laclaustra, M., Pocock, S., Mocoroa, A., Mendiguren, J.M., Sanz, G., Guallar, E., Bansilal, S., Vedanthan, R., Jimenez-Borreguero, L.J., Ibanez, B., Ordovas, J.M., Fernandez-Ortiz, A., Bueno, H., Fuster, V. 2016. Association between a social-business eating pattern and early asymptomatic atherosclerosis. Journal of the American College of Cardiology. doi: 10.1016/j.jacc.2016.05.080.
Garaulet, M., Vera, B., Bonnet-Rubio, G., Gómez-Abellán, P., Lee, Y., Ordovas, J.M. 2016. Lunch eating predicts weight-loss effectiveness in carriers of the common allele at PERILIPIN1: the ONTIME (Obesity, Nutrigenetics, Timing, Mediterranean) study. American Journal of Clinical Nutrition. doi: 10.3945/ajcn.116.134528.
Garcia-Rios, A., Alcala-Diaz, J.F., Gomez-Delgado, F., Delgado-Lista, J., Marin, C., Leon-Acuna, A., Camargo, A., Rodriguez-Cantalego, F., Blanco-Rojo, R., Quintana-Navarro, G., Ordovas, J.M., Perez-Jimenez, F., Lopez-Mirando, J., Perez-Martinez, P. 2016. Beneficial effect of CETP gene polymorphism in combination with a Mediterranean diet influencing lipid metabolism in metabolic syndrome patients: CORDIOPREV study. Clinical Nutrition. doi: 10.1016/j.clnu.2016.12.011.
Sayols-Baixeras, S., Subirana, I., Lluis-Ganella, C., Civeira, F., Roquer, J., Do, A., Absher, D., Cenarro, A., Munoz, D., Soriano-Tarraga, C., Jimenez-Conde, J., Ordovas, J.M., Senti, M., Aslibekyan, S., Marrugat, J., Arnett, D.K., Elosua, R. 2016. Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study. Human Molecular Genetics. 25(20):4556-4565. doi: 10.1093/hmg/ddw285.
Cerqueria-Cezar, C., Pedersen, K., Calero-Bernal, R., Kwok, O.C., Villena, I., Dubey, J.P. 2016. Seroprevalence of Neospora caninum in feral swine (Sus scrofa) in the United States. Veterinary Parasitology. 226:35-37.
Smith, C.E., Coltell, O., Sorli, J.V., Estruch, R., Martinez-Gonzalez, M., Salas-Salvado, J., Fito, M., Aros, F., Dashti, H.S., Lai, C., Miro, L., Serra-Majem, L., Gomez-Gracia, E., Fiol, M., Ros, E., Aslibekyan, S., Hidalgo, B., Neuhouser, M., Di, C., Tucker, K., Arnett, D.K., Ordovas, J.M., Corella, D. 2016. Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization. Scientific Reports. doi: 10.1038/srep33188.
Blanco-Rojo, R., Delgado-Lista, J., Lee, Y., Lai, C., Perez-Martinez, P., Rangel-Zuniga, O., Smith, C.E., Hidalgo, B., Alcala-Diaz, J.F., Gomez-Delgado, F., Parnell, L.D., Arnett, D.K., Tucker, K.L., Lopez-Miranda, J., Ordovas, J.M. 2016. Interaction of an S100A9 gene variant with saturated fat and carbohydrates to modulate insulin resistance in 3 populations of different ancestries. American Journal of Clinical Nutrition. 104:508–517.
Hurtado-Roca, Y., Bueno, H., Fernandez-Ortiz, A., Ordovas, J., Ibanez, B., Fuster, V., Rodriquez-Artalejo, F., Laclaustra, M. 2017. Ordovas-Oxidized LDL is associated with metabolic syndrome traits independently of central obesity and insulin resistance. Diabetes. doi: 10.2337/db16-0933.
Richardson, K., Schnitzler, G.R., Lai, C., Ordovas, J.M. 2015. Functional genomics analysis of big data identifies novel peroxisome proliferator–activated receptor gamma target single nucleotide polymorphisms showing association with cardiometabolic outcomes. Circulation: Cardiovascular Genetics. 8:842-851. doi: 10.1161/CIRCGENETICS.115.001174.
Johnston, J.D., Ordovas, J.M., Scheer, F.A., Turek, F.W. 2016. Circadian rhythms, metabolism, and chrononutrition in rodents and humans. Advances in Nutrition. doi: 10.3945/an.115.010777.
Smith, C.E., Fuillerton, S.M., Dookeran, K.A., Hampel, H., Tin, A., Maruthur, N.M., Schisler, J.C., Henderson, J.A., Tucker, K.L., Ordovas, J.M. 2016. Using genetic technologies to reduce, rather than widen, health disparities. Health Affairs. 35(8):1367-1373.
Dashti, H.S., Scheer, F.A., Jacques, P.F., Lamon-Fava, S., Ordovas, J.M. 2015. Short sleep duration and dietary intake: epidemiologic evidence, mechanisms, and health implications. Advances in Nutrition. 6:648–659. doi: 10.3945/an.115.008623.