{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T10:35:26Z","timestamp":1756636526209},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Cardiovascular risk factors tend to aggregate. The biological and predictive value of this aggregation is questioned and genetics could shed light on this debate. Our aims were to reappraise the impact of risk factor confluence on ischemic heart disease (IHD) risk by testing whether genetic risk scores (GRSs) associated with these factors interact on an additive or multiplicative scale, and to determine whether these interactions provide additional value for predicting IHD risk.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We selected genetic variants associated with blood pressure, body mass index, waist circumference, triglycerides, type-2 diabetes mellitus, high-density lipoprotein and low-density lipoprotein cholesterol, and IHD to create GRSs for each factor. We tested and meta-analyzed the impact of additive (synergy index) and multiplicative (\u03b2\n              <jats:sub>interaction<\/jats:sub>\n              ) interactions between each GRS pair in 1 case\u2013control (n=6042) and 4 cohort studies (n=17\u2009794) and evaluated the predictive value of these interactions. We observed 2 multiplicative interactions: GRS\n              <jats:sub>LDL<\/jats:sub>\n              \u00b7GRS\n              <jats:sub>Triglycerides<\/jats:sub>\n              (\u03b2\n              <jats:sub>interaction<\/jats:sub>\n              =\u20130.096; SE=0.028) and nonpleiotropic GRS\n              <jats:sub>IHD<\/jats:sub>\n              \u00b7GRS\n              <jats:sub>LDL<\/jats:sub>\n              (\u03b2\n              <jats:sub>interaction<\/jats:sub>\n              =0.091; SE=0.028). Inclusion of these interaction terms did not improve predictive capacity.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The confluence of low-density lipoprotein cholesterol and triglycerides genetic risk load has an additive effect on IHD risk. The interaction between low-density lipoprotein cholesterol and IHD genetic load is more than multiplicative, supporting the hazardous impact on atherosclerosis progression of the combination of inflammation and increased lipid levels. The capacity of risk factor confluence to improve IHD risk prediction is questionable. Further studies in larger samples are warranted to confirm and expand our results.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.115.001255","type":"journal-article","created":{"date-parts":[[2016,4,22]],"date-time":"2016-04-22T03:38:34Z","timestamp":1461296314000},"page":"279-286","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Cardiovascular Risk Factors and Ischemic Heart Disease"],"prefix":"10.1161","volume":"9","author":[{"given":"Roberto","family":"Elosua","sequence":"first","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Llu\u00eds-Ganella","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac","family":"Subirana","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aki","family":"Havulinna","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristi","family":"L\u00e4ll","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Lucas","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergi","family":"Sayols-Baixeras","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arto","family":"Pietil\u00e4","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maris","family":"Alver","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Cabrera de Le\u00f3n","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariano","family":"Sent\u00ed","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Siscovick","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olle","family":"Mellander","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krista","family":"Fischer","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veikko","family":"Salomaa","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaume","family":"Marrugat","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain (R.E., C.L.-G., I.S., G.L., S.S.-B., J.M.); Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain (I.S.); National Institute for Health and Welfare, Helsinki, Finland (A.H., A.P., V.S.); Estonian Genome Center of Tartu University, Tartu, Estonia (K.L., M.A., K.F.); Research Unit, Nuestra Se\u00f1ora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain (A.C.d.L.); University of La Laguna, La Laguna,..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-55-1-33"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1157\/13116658"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.192644"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.09.032"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.05.034"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.048611"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.9.2289"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJR.0b013e3283282f8d"},{"key":"e_1_3_4_10_2","unstructured":"Hindorff LA MacArthur J Morales J Junkins HA Hall PN Klemm AK et al. A Catalog of Published Genome-Wide Association Studies. www.genome.gov\/gwastudies. Accessed January 15 2013."},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt093"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv108"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.327"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt268"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2797"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10405"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.922"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2897"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14177"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14132"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3396"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13595"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000529"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11632"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1515\/em-2013-0005"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dym157"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwg113"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2540.2001.00901.x"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X0600600302"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4085"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4026"},{"key":"e_1_3_4_34_2","volume-title":"R: A language and environment for statistical computing","author":"Team RDC","year":"2010","unstructured":"Team RDC. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2010."},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003919"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.5271\/sjweh.2106"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61177-6"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2480"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306471"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3793"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.5.1210"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.18.1837"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.79.3.248"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000080897.52664.94"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.11.2676"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2003.09.028"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.2.385"}],"container-title":["Circulation: Cardiovascular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGENETICS.115.001255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:20:47Z","timestamp":1715563247000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGENETICS.115.001255"}},"subtitle":["Is the Confluence of Risk Factors Greater Than the Parts? A Genetic Approach"],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1161\/CIRCGENETICS.115.001255"],"URL":"https:\/\/doi.org\/10.1161\/circgenetics.115.001255","relation":{},"ISSN":["1942-325X","1942-3268"],"issn-type":[{"value":"1942-325X","type":"print"},{"value":"1942-3268","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6]]}}}