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3. Repeated Psychosocial Screening of High School Students Using YouthCHAT: Cohort Study

Author

Thabrew, Hiran, Kumar, Harshali, Goldfinch, Mary, Cavadino, Alana, and Goodyear-Smith, Felicity

Subjects
Pediatrics, RJ1-570
Abstract

BackgroundPsychosocial problems are common during adolescence and can have long-lasting effects on health and on academic and social functioning. YouthCHAT, an electronic HEEADSSS (home, education, eating, activities, drugs and alcohol, suicide and depression, sexuality and safety)-aligned instrument, has recently been demonstrated to be an acceptable and effective school-based psychosocial screener for 13-year-old (Year 9) high school students. ObjectiveThis study aims to compare acceptability and detection rates with repeated YouthCHAT screenings of high school students when they are 13 years old (Year 9) and 14 years old (Year 10). MethodsWe invited all Year-10 students to complete a YouthCHAT screening in 2018. Rates of positively identified issues were compared between the subset of students screened in both 2017 and 2018. Student acceptability toward YouthCHAT was investigated through focus group sessions. Onward clinical referral rates in 2018 were also investigated to explore the potential referral burden following screening. Data analysis for rates of positively identified issues were conducted with the McNemar test. Chi-square, Fisher exact test, and Kruskal-Wallis test were used to analyze the focus group data. ResultsOf 141 eligible Year-10 students, 114 (81%) completed a YouthCHAT screening during 2018, and 97 (85%) of them completed it for a second time. Apart from depression, which increased (P=.002), and perceived life stress, which decreased (P=.04), rates of identified issues were broadly similar between 13 and 14 years of age. Repeated screenings via YouthCHAT was acceptable to students and time-efficient (mean, 6 minutes and 32 seconds) but did not reduce the overall number of individuals with identified issues. Onward clinical referrals from positive screens were mostly managed by school-based health services without the need for external referrals. ConclusionsAlthough further evaluation is needed, our results support the value of YouthCHAT as an acceptable and effective instrument with which to achieve routine identification of psychosocial issues and early intervention within a high school environment.

Published
2020
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4. Coping Skills Mobile App to Support the Emotional Well-Being of Young People During the COVID-19 Pandemic: Protocol for a Mixed Methods Study

Author

Serlachius, Anna, Schache, Kiralee, Boggiss, Anna, Lim, David, Wallace-Boyd, Kate, Brenton-Peters, Jennifer, Buttenshaw, Elise, Chadd, Stephanie, Cavadino, Alana, Cao, Nicholas, Morunga, Eva, and Thabrew, Hiran

Subjects
Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundThe COVID-19 pandemic is likely to increase anxiety and distress in young people worldwide. It is important to prioritize mental health during crisis events to mitigate the negative and often long-term effects of the crises on young people, families, and society. Mental health and well-being apps represent a scalable approach for improving psychological outcomes in young people and have potential to improve the equity of service access. ObjectiveThe Whitu: 7 Ways in 7 Days well-being app was recently developed by our group to address the urgent need for innovative approaches to reach young New Zealanders who are struggling to cope with the COVID-19 pandemic. The aim of this study is twofold: to evaluate the acceptability of the prototype app and to examine the effectiveness of the refined app at improving mental and emotional well-being and reducing depression, anxiety, and stress in young people in New Zealand. MethodsA two-phase mixed methods study will be undertaken to achieve these aims. During the first phase, 20 young people aged 16-30 years (including those of Māori and Pacific ethnicity) will participate in a qualitative study to help refine the prototype app. During the second phase, 90 young people aged 16-30 years will participate in a randomized waitlist-controlled trial (RCT) to evaluate the efficacy of the refined Whitu app at 4 weeks and 3 months after baseline. Outcomes will be evaluated using validated web-based questionnaires at baseline, 4 weeks, and 3 months. ResultsThe study received ethics approval in May 2020, and recruitment for the focus groups commenced in June 2020. Recruitment for the RCT is expected to commence in October 2020. Participants for both study phases will be recruited via social media and web-based communities. Data collection for the RCT is expected to be completed by January 2021, and analyses are expected to be completed by March 2021. Linear mixed modelling will be used to determine between-group differences in psychological outcomes. ConclusionsThere is an urgent need to develop culturally appropriate, scalable mental health interventions to address the psychological consequences of the COVID-19 pandemic. In this study, we will develop and test an evidence-based well-being app that, if effective, can be made available to all young people in New Zealand and internationally. Trial RegistrationAustralian New Zealand Clinical Trials Registry (ACTRN12620000516987); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379597. International Registered Report Identifier (IRRID)PRR1-10.2196/23716

Published
2020
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6. LSDDEP2: study protocol for a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients with major depressive disorder

Author

Daldegan-Bueno, Dimitri, Donegan, Carina Joy, Forsyth, Anna, Sumner, Rachael Louise, Murphy, Robin J., Menkes, David B., Evans, William, Hoeh, Nicholas, Sundram, Frederick, Reynolds, Lisa M., Ponton, Rhys, Cavadino, Alana, Smith, Todd, Roop, Partha, Allen, Nathan, Abeysinghe, Binu, Svirskis, Darren, Bansal, Mahima, and Muthukumaraswamy, Suresh

Published
2024
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10. An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1)

Author

Donegan, Carina Joy, Daldegan-Bueno, Dimitri, Sumner, Rachael, Menkes, David, Evans, William, Hoeh, Nicholas, Sundram, Frederick, Reynolds, Lisa, Ponton, Rhys, Cavadino, Alana, Smith, Todd, Roop, Partha, Allen, Nathan, Abeysinghe, Binu, Svirskis, Darren, Forsyth, Anna, Bansal, Mahima, and Muthukumaraswamy, Suresh

Published
2023
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22. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author

Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Morgen, Camilla S, van Kampen, Antoine HC, van Schaik, Barbera DC, Mentch, Frank D, Langenberg, Claudia, Luan, Jian’an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil VR, Fonvig, Cilius E, and Trier, Caecilie

Subjects
Biological Sciences, Genetics, Cardiovascular, Perinatal Period - Conditions Originating in Perinatal Period, Nutrition, Prevention, Preterm, Low Birth Weight and Health of the Newborn, Pediatric, Obesity, Conditions Affecting the Embryonic and Fetal Periods, Infant Mortality, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Adult, Birth Weight, Blood Pressure, Body Height, Diabetes Mellitus, Type 2, Female, Fetal Development, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Diseases, Humans, Infant, Newborn, Male, Maternal Inheritance, Maternal-Fetal Exchange, Metabolic Diseases, Models, Genetic, Polymorphism, Single Nucleotide, Pregnancy, Risk Factors, EGG Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Published
2019

27. Hierarchical models in the analysis of trends in prevalence of congenital anomalies and risks associated with first trimester medications

Author

Cavadino, Alana

Subjects
616
Abstract

Background: Early identification of risk factors, in particular first trimester teratogenic medications, for congenital anomalies (CAs) is essential. Despite similarities between different CAs and between different medications, current surveillance methods in Europe examine each CA and each medication separately. This thesis aims to investigate whether the use of hierarchical statistical methods combining information in groups can improve CA surveillance methods. Methods: EUROCAT is a European network of population-based CA registries, with EUROmediCAT comprising those registries with additional information on medication use in pregnancy. Trends in CAs from 2003-2012 in 18 EUROCAT registries (n=81,147) were analysed using Poisson regression models considering each CA separately and using hierarchical models combining related subgroups. First trimester medication exposures from 1995-2011 in 13 EUROmediCAT registries (n=15,058) were analysed. Firstly, groupings of medications and/or CAs were considered when determining the statistical significance of each medication-CA combination, using False Discovery Rate (FDR) procedures to adjust for multiple testing. Secondly, Bayesian hierarchical models were applied to directly model the group effects. The Australian classification system for prescribing medicines in pregnancy was used to independently identify "high risk" medications. The number of "high risk" medications identified by the FDR methods and Bayesian models were compared. Results: For analysis of trends, grouping EUROCAT CA subgroups using hierarchical models did not provide additional information over that obtained from independent analyses of each subgroup. The double FDR method grouping medications by ATC3 level codes performed better than other FDR methods. Use of Bayesian hierarchical models did not produce enough of an improvement to justify the increased effort of implementing such models.

Published
2018

30. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Author

Jiang, Xia, O’Reilly, Paul F, Aschard, Hugues, Hsu, Yi-Hsiang, Richards, J Brent, Dupuis, Josée, Ingelsson, Erik, Karasik, David, Pilz, Stefan, Berry, Diane, Kestenbaum, Bryan, Zheng, Jusheng, Luan, Jianan, Sofianopoulou, Eleni, Streeten, Elizabeth A, Albanes, Demetrius, Lutsey, Pamela L, Yao, Lu, Tang, Weihong, Econs, Michael J, Wallaschofski, Henri, Völzke, Henry, Zhou, Ang, Power, Chris, McCarthy, Mark I, Michos, Erin D, Boerwinkle, Eric, Weinstein, Stephanie J, Freedman, Neal D, Huang, Wen-Yi, Van Schoor, Natasja M, van der Velde, Nathalie, Groot, Lisette CPGM de, Enneman, Anke, Cupples, L Adrienne, Booth, Sarah L, Vasan, Ramachandran S, Liu, Ching-Ti, Zhou, Yanhua, Ripatti, Samuli, Ohlsson, Claes, Vandenput, Liesbeth, Lorentzon, Mattias, Eriksson, Johan G, Shea, M Kyla, Houston, Denise K, Kritchevsky, Stephen B, Liu, Yongmei, Lohman, Kurt K, Ferrucci, Luigi, Peacock, Munro, Gieger, Christian, Beekman, Marian, Slagboom, Eline, Deelen, Joris, Heemst, Diana van, Kleber, Marcus E, März, Winfried, de Boer, Ian H, Wood, Alexis C, Rotter, Jerome I, Rich, Stephen S, Robinson-Cohen, Cassianne, den Heijer, Martin, Jarvelin, Marjo-Riitta, Cavadino, Alana, Joshi, Peter K, Wilson, James F, Hayward, Caroline, Lind, Lars, Michaëlsson, Karl, Trompet, Stella, Zillikens, M Carola, Uitterlinden, Andre G, Rivadeneira, Fernando, Broer, Linda, Zgaga, Lina, Campbell, Harry, Theodoratou, Evropi, Farrington, Susan M, Timofeeva, Maria, Dunlop, Malcolm G, Valdes, Ana M, Tikkanen, Emmi, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Raitakari, Olli T, Mikkilä, Vera, Ikram, M Arfan, Sattar, Naveed, Jukema, J Wouter, Wareham, Nicholas J, Langenberg, Claudia, Forouhi, Nita G, Gundersen, Thomas E, Khaw, Kay-Tee, Butterworth, Adam S, Danesh, John, and Spector, Timothy

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Amidohydrolases, Autoimmune Diseases, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Vesicular Transport Proteins, Vitamin D, White People
Abstract

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Published
2018

32. DIGIPREDICT: physiological, behavioural and environmental predictors of asthma attacks—a prospective observational study using digital markers and artificial intelligence—study protocol

Author

Chan, Amy Hai Yan, primary, Te Ao, Braden, additional, Baggott, Christina, additional, Cavadino, Alana, additional, Eikholt, Amber A, additional, Harwood, Matire, additional, Hikaka, Joanna, additional, Gibbs, Dianna, additional, Hudson, Mariana, additional, Mirza, Farhaan, additional, Naeem, Muhammed Asif, additional, Semprini, Ruth, additional, Chang, Catherina L, additional, Tsang, Kevin C H, additional, Shah, Syed Ahmar, additional, Jeremiah, Aron, additional, Abeysinghe, Binu Nisal, additional, Roy, Rajshri, additional, Wall, Clare, additional, Wood, Lisa, additional, Dalziel, Stuart, additional, Pinnock, Hilary, additional, van Boven, Job F M, additional, Roop, Partha, additional, and Harrison, Jeff, additional

Published
2024
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35. Signal Detection in EUROmediCAT: Identification and Evaluation of Medication–Congenital Anomaly Associations and Use of VigiBase as a Complementary Source of Reference

Author

Cavadino, Alana, Sandberg, Lovisa, Öhman, Inger, Bergvall, Tomas, Star, Kristina, Dolk, Helen, Loane, Maria, Addor, Marie-Claude, Barisic, Ingeborg, Cavero-Carbonell, Clara, Garne, Ester, Gatt, Miriam, Khoshnood, Babak, Klungsøyr, Kari, Latos-Bielenska, Anna, Lelong, Nathalie, Lutke, Reneé, Materna-Kiryluk, Anna, Nelen, Vera, Nevill, Amanda, O’Mahony, Mary, Mokoroa, Olatz, Pierini, Anna, Randrianaivo, Hanitra, Rissmann, Anke, Tucker, David, Wiesel, Awi, Yevtushok, Lyubov, and Morris, Joan K

Published
2021
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37. Association of ethnicity with unintentional injury‐related hospitalisation and mortality among older people residing in two regions of Aotearoa New Zealand.

Author

Dwight, Emily, Cavadino, Alana, Kool, Bridget, Kerse, Ngaire, and Hikaka, Joanna

Subjects
WOUNDS & injuries, HEALTH services accessibility, RESEARCH funding, HOSPITAL care, SCIENTIFIC observation, DESCRIPTIVE statistics, AGE distribution, CONFIDENCE intervals, ACCIDENTAL falls, OLD age
Abstract

Objectives: To characterise unintentional injury‐related hospitalisation and mortality amongst older adults (aged 50+ years) in the Lakes and Bay of Plenty District Health Boards of Aotearoa New Zealand and to examine whether hospitalisation patterns differed by ethnicity. Methods: This observational study analysed unintentional injury‐related hospitalisations and deaths among older adults between 2014 and 2018. Routinely collected national data sets were used to calculate annualised, age‐standardised injury rates. The independent variable of interest was ethnicity (Māori or non‐Māori). Results: There were 11,834 unintentional injury‐related hospitalisations in the study period (n = 1444 for Māori). Overall, there was no significant difference in the age‐standardised hospitalisation rate between Māori and non‐Māori (Standardised Rate Ratio [SRR] = 0.96 [95% CI 0.90, 1.02]). Falls were the most common mechanism of injury among Māori and non‐Māori overall (50% and 71%) and relative risks of falls increased with age. Non‐Māori were 57% less likely to be hospitalised for unintentional poisoning than Māori (SRR = 0.43, [0.34, 0.59]). Conclusions: The mechanisms of injury, and variation in unintentional injury‐related hospitalisation rates between Māori and non‐Māori, change throughout older age, and incidence increase0073 with age. Falls cause significant injury‐related hospitalisations for older Māori and responsive injury prevention and rehabilitation efforts are warranted to achieve equitable health outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Author

Okbay, Aysu, Baselmans, Bart ML, De Neve, Jan-Emmanuel, Turley, Patrick, Nivard, Michel G, Fontana, Mark Alan, Meddens, S Fleur W, Linnér, Richard Karlsson, Rietveld, Cornelius A, Derringer, Jaime, Gratten, Jacob, Lee, James J, Liu, Jimmy Z, de Vlaming, Ronald, Ahluwalia, Tarunveer S, Buchwald, Jadwiga, Cavadino, Alana, Frazier-Wood, Alexis C, Furlotte, Nicholas A, Garfield, Victoria, Geisel, Marie Henrike, Gonzalez, Juan R, Haitjema, Saskia, Karlsson, Robert, van der Laan, Sander W, Ladwig, Karl-Heinz, Lahti, Jari, van der Lee, Sven J, Lind, Penelope A, Liu, Tian, Matteson, Lindsay, Mihailov, Evelin, Miller, Michael B, Minica, Camelia C, Nolte, Ilja M, Mook-Kanamori, Dennis, van der Most, Peter J, Oldmeadow, Christopher, Qian, Yong, Raitakari, Olli, Rawal, Rajesh, Realo, Anu, Rueedi, Rico, Schmidt, Börge, Smith, Albert V, Stergiakouli, Evie, Tanaka, Toshiko, Taylor, Kent, Thorleifsson, Gudmar, Wedenoja, Juho, Wellmann, Juergen, Westra, Harm-Jan, Willems, Sara M, Zhao, Wei, Amin, Najaf, Bakshi, Andrew, Bergmann, Sven, Bjornsdottir, Gyda, Boyle, Patricia A, Cherney, Samantha, Cox, Simon R, Davies, Gail, Davis, Oliver SP, Ding, Jun, Direk, Nese, Eibich, Peter, Emeny, Rebecca T, Fatemifar, Ghazaleh, Faul, Jessica D, Ferrucci, Luigi, Forstner, Andreas J, Gieger, Christian, Gupta, Richa, Harris, Tamara B, Harris, Juliette M, Holliday, Elizabeth G, Hottenga, Jouke-Jan, De Jager, Philip L, Kaakinen, Marika A, Kajantie, Eero, Karhunen, Ville, Kolcic, Ivana, Kumari, Meena, Launer, Lenore J, Franke, Lude, Li-Gao, Ruifang, Liewald, David C, Koini, Marisa, Loukola, Anu, Marques-Vidal, Pedro, Montgomery, Grant W, Mosing, Miriam A, Paternoster, Lavinia, Pattie, Alison, Petrovic, Katja E, Pulkki-Råback, Laura, Quaye, Lydia, Räikkönen, Katri, Rudan, Igor, and Scott, Rodney J

Subjects
Biological Sciences, Genetics, Mental Health, Human Genome, Depression, Anxiety Disorders, Bayes Theorem, Genome-Wide Association Study, Humans, Neuroticism, Phenotype, Polymorphism, Single Nucleotide, LifeLines Cohort Study, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

Published
2016

44. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.

Author

Holmes, Michael V, Dale, Caroline E, Zuccolo, Luisa, Silverwood, Richard J, Guo, Yiran, Ye, Zheng, Prieto-Merino, David, Dehghan, Abbas, Trompet, Stella, Wong, Andrew, Cavadino, Alana, Drogan, Dagmar, Padmanabhan, Sandosh, Li, Shanshan, Yesupriya, Ajay, Leusink, Maarten, Sundstrom, Johan, Hubacek, Jaroslav A, Pikhart, Hynek, Swerdlow, Daniel I, Panayiotou, Andrie G, Borinskaya, Svetlana A, Finan, Chris, Shah, Sonia, Kuchenbaecker, Karoline B, Shah, Tina, Engmann, Jorgen, Folkersen, Lasse, Eriksson, Per, Ricceri, Fulvio, Melander, Olle, Sacerdote, Carlotta, Gamble, Dale M, Rayaprolu, Sruti, Ross, Owen A, McLachlan, Stela, Vikhireva, Olga, Sluijs, Ivonne, Scott, Robert A, Adamkova, Vera, Flicker, Leon, Bockxmeer, Frank M van, Power, Christine, Marques-Vidal, Pedro, Meade, Tom, Marmot, Michael G, Ferro, Jose M, Paulos-Pinheiro, Sofia, Humphries, Steve E, Talmud, Philippa J, Mateo Leach, Irene, Verweij, Niek, Linneberg, Allan, Skaaby, Tea, Doevendans, Pieter A, Cramer, Maarten J, van der Harst, Pim, Klungel, Olaf H, Dowling, Nicole F, Dominiczak, Anna F, Kumari, Meena, Nicolaides, Andrew N, Weikert, Cornelia, Boeing, Heiner, Ebrahim, Shah, Gaunt, Tom R, Price, Jackie F, Lannfelt, Lars, Peasey, Anne, Kubinova, Ruzena, Pajak, Andrzej, Malyutina, Sofia, Voevoda, Mikhail I, Tamosiunas, Abdonas, Maitland-van der Zee, Anke H, Norman, Paul E, Hankey, Graeme J, Bergmann, Manuela M, Hofman, Albert, Franco, Oscar H, Cooper, Jackie, Palmen, Jutta, Spiering, Wilko, de Jong, Pim A, Kuh, Diana, Hardy, Rebecca, Uitterlinden, Andre G, Ikram, M Arfan, Ford, Ian, Hyppönen, Elina, Almeida, Osvaldo P, Wareham, Nicholas J, Khaw, Kay-Tee, Hamsten, Anders, Husemoen, Lise Lotte N, Tjønneland, Anne, Tolstrup, Janne S, Rimm, Eric, Beulens, Joline WJ, and Verschuren, WM Monique

Subjects
InterAct Consortium, Humans, Coronary Disease, Alcohol Dehydrogenase, Genetic Markers, Models, Statistical, Alcohol Drinking, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Stroke, Mendelian Randomization Analysis, Biomarkers, General & Internal Medicine, Clinical Sciences, Public Health and Health Services
Abstract

ObjectiveTo use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.DesignMendelian randomisation meta-analysis of 56 epidemiological studies.Participants261 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 measuresOdds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.ResultsCarriers 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)).ConclusionsIndividuals 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.

Published
2014

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