08212nas a2202197 4500008004100000022001400041245013100055210006900186260001600255300001000271490000800281520207900289653001002368653000902378653002602387653002102413653001502434653002102449653001102470653002002481653001302501653001102514653000902525653003702534653001602571653002402587653003602611653001102647100002302658700002202681700001902703700002702722700001502749700001402764700002502778700001902803700002002822700001702842700002002859700001902879700002502898700001702923700002002940700002102960700002202981700002503003700001903028700002403047700002603071700002803097700001703125700001603142700003103158700001503189700002003204700002103224700001803245700002003263700001903283700002403302700002003326700002103346700001803367700002103385700002003406700001903426700002103445700001903466700001803485700002803503700002103531700002503552700001503577700002303592700001903615700002703634700002403661700002403685700002403709700001803733700002103751700001603772700002603788700002303814700001503837700002103852700002303873700002403896700001803920700002603938700002203964700001903986700001804005700001804023700002104041700001904062700001704081700002104098700001904119700002104138700002404159700002404183700003404207700002004241700002204261700002504283700001904308700002104327700001904348700001804367700002004385700002004405700001504425700001904440700002804459700002004487700001404507700002104521700002404542700002504566700001804591700002004609700002804629700002204657700002304679700001504702700002504717700002904742700003104771700002204802700002204824700002204846700002004868700002304888700001804911700002004929700001904949700001904968700002504987700002205012700002005034700002405054700002305078700001805101700002505119700002405144700002005168700001905188700001805207700001505225700002205240700002505262700002005287700002105307700002105328700001905349700002305368700002205391700002205413700002205435700002105457700002505478700001905503700002705522700001905549700002205568700002005590700002505610700002105635700002005656700002105676700002105697700002005718700002405738700002805762700001805790700001905808700002405827700001905851700002005870700002405890700002105914700001905935710002405954856003605978 2014 eng d a1756-183300aAssociation between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.0 aAssociation between alcohol and cardiovascular disease Mendelian c2014 Jul 10 ag41640 v3493 a
OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.
DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies.
PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.
MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.
RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).
CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.
10aAdult10aAged10aAlcohol Dehydrogenase10aAlcohol Drinking10aBiomarkers10aCoronary Disease10aFemale10aGenetic Markers10aGenotype10aHumans10aMale10aMendelian Randomization Analysis10aMiddle Aged10aModels, Statistical10aPolymorphism, Single Nucleotide10aStroke1 aHolmes, Michael, V1 aDale, Caroline, E1 aZuccolo, Luisa1 aSilverwood, Richard, J1 aGuo, Yiran1 aYe, Zheng1 aPrieto-Merino, David1 aDehghan, Abbas1 aTrompet, Stella1 aWong, Andrew1 aCavadino, Alana1 aDrogan, Dagmar1 aPadmanabhan, Sandosh1 aLi, Shanshan1 aYesupriya, Ajay1 aLeusink, Maarten1 aSundström, Johan1 aHubacek, Jaroslav, A1 aPikhart, Hynek1 aSwerdlow, Daniel, I1 aPanayiotou, Andrie, G1 aBorinskaya, Svetlana, A1 aFinan, Chris1 aShah, Sonia1 aKuchenbaecker, Karoline, B1 aShah, Tina1 aEngmann, Jorgen1 aFolkersen, Lasse1 aEriksson, Per1 aRicceri, Fulvio1 aMelander, Olle1 aSacerdote, Carlotta1 aGamble, Dale, M1 aRayaprolu, Sruti1 aRoss, Owen, A1 aMcLachlan, Stela1 aVikhireva, Olga1 aSluijs, Ivonne1 aScott, Robert, A1 aAdamkova, Vera1 aFlicker, Leon1 avan Bockxmeer, Frank, M1 aPower, Christine1 aMarques-Vidal, Pedro1 aMeade, Tom1 aMarmot, Michael, G1 aFerro, Jose, M1 aPaulos-Pinheiro, Sofia1 aHumphries, Steve, E1 aTalmud, Philippa, J1 aLeach, Irene, Mateo1 aVerweij, Niek1 aLinneberg, Allan1 aSkaaby, Tea1 aDoevendans, Pieter, A1 aCramer, Maarten, J1 aHarst, Pim1 aKlungel, Olaf, H1 aDowling, Nicole, F1 aDominiczak, Anna, F1 aKumari, Meena1 aNicolaides, Andrew, N1 aWeikert, Cornelia1 aBoeing, Heiner1 aEbrahim, Shah1 aGaunt, Tom, R1 aPrice, Jackie, F1 aLannfelt, Lars1 aPeasey, Anne1 aKubinova, Ruzena1 aPajak, Andrzej1 aMalyutina, Sofia1 aVoevoda, Mikhail, I1 aTamosiunas, Abdonas1 avan der Zee, Anke, H Maitland1 aNorman, Paul, E1 aHankey, Graeme, J1 aBergmann, Manuela, M1 aHofman, Albert1 aFranco, Oscar, H1 aCooper, Jackie1 aPalmen, Jutta1 aSpiering, Wilko1 ade Jong, Pim, A1 aKuh, Diana1 aHardy, Rebecca1 aUitterlinden, André, G1 aIkram, Arfan, M1 aFord, Ian1 aHyppönen, Elina1 aAlmeida, Osvaldo, P1 aWareham, Nicholas, J1 aKhaw, Kay-Tee1 aHamsten, Anders1 aHusemoen, Lise, Lotte N1 aTjønneland, Anne1 aTolstrup, Janne, S1 aRimm, Eric1 aBeulens, Joline, W J1 aVerschuren, W, M Monique1 aOnland-Moret, Charlotte, N1 aHofker, Marten, H1 aWannamethee, Goya1 aWhincup, Peter, H1 aMorris, Richard1 aVicente, Astrid, M1 aWatkins, Hugh1 aFarrall, Martin1 aJukema, Wouter1 aMeschia, James1 aCupples, Adrienne, L1 aSharp, Stephen, J1 aFornage, Myriam1 aKooperberg, Charles1 aLaCroix, Andrea, Z1 aDai, James, Y1 aLanktree, Matthew, B1 aSiscovick, David, S1 aJorgenson, Eric1 aSpring, Bonnie1 aCoresh, Josef1 aLi, Yun, R1 aBuxbaum, Sarah, G1 aSchreiner, Pamela, J1 aEllison, Curtis1 aTsai, Michael, Y1 aPatel, Sanjay, R1 aRedline, Susan1 aJohnson, Andrew, D1 aHoogeveen, Ron, C1 aHakonarson, Hakon1 aRotter, Jerome, I1 aBoerwinkle, Eric1 ade Bakker, Paul, I W1 aKivimaki, Mika1 aAsselbergs, Folkert, W1 aSattar, Naveed1 aLawlor, Debbie, A1 aWhittaker, John1 aSmith, George, Davey1 aMukamal, Kenneth1 aPsaty, Bruce, M1 aWilson, James, G1 aLange, Leslie, A1 aHamidovic, Ajna1 aHingorani, Aroon, D1 aNordestgaard, Børge, G1 aBobak, Martin1 aLeon, David, A1 aLangenberg, Claudia1 aPalmer, Tom, M1 aReiner, Alex, P1 aKeating, Brendan, J1 aDudbridge, Frank1 aCasas, Juan, P1 aInterAct Consortium uhttps://chs-nhlbi.org/node/6569