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A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations
- Penelope A. Lind, Stuart Macgregor, Jacqueline M. Vink, Michele L Pergadia, Narelle K. Hansell, Marleen H. M. de Moor, August B. Smit, Jouke-Jan Hottenga, Melinda M. Richter, Andrew C. Heath, Nicholas G. Martin, Gonneke Willemsen, Eco J. C. de Geus, Nicole Vogelzangs, Brenda W. Penninx, John B. Whitfield, Grant W. Montgomery, Dorret I. Boomsma, Pamela A. F. Madden
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- Journal:
- Twin Research and Human Genetics / Volume 13 / Issue 1 / February 2010
- Published online by Cambridge University Press:
- 21 January 2016, pp. 11-29
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Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10, 000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10-8) for ND (rs964170 in ARHGAPlOon chromosome 4, p = 4.43 x 10”8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10-9), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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Notes on Contributors
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- By Adam H. Becker, Michael Bernard-Donals, Mary Cappello, Maria DiBattista, Leland de la Durantaye, John V. Fleming, Eli Friedlander, Alastair Hannay, Trudier Harris, Lawrence D. Kritzman, Alfred MacAdam, Patrick Madden, Deborah Epstein Nord, Jean-Michel Rabaté, Robert F. Sayre, Frances Wilson, Emily O. Wittman
- Edited by Maria DiBattista, Princeton University, New Jersey, Emily O. Wittman, University of Alabama, Tuscaloosa
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- The Cambridge Companion to Autobiography
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- 05 May 2014
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- 22 May 2014, pp ix-xii
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Long-Term Stability and Heritability of Telephone Interview Measures of Alcohol Consumption and Dependence
- Narelle K. Hansell, Arpana Agrawal, John B. Whitfield, Katherine I. Morley, Gu Zhu, Penelope A. Lind, Michele L. Pergadia, Pamela A. F. Madden, Richard D. Todd, Andrew C. Heath, Nicholas G. Martin
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- Journal:
- Twin Research and Human Genetics / Volume 11 / Issue 3 / 01 June 2008
- Published online by Cambridge University Press:
- 21 February 2012, pp. 287-305
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Alcohol dependence symptoms and consumption measures were examined for stability and heritability. Data were collected from 12,045 individuals (5376 twin pairs, 1293 single twins) aged 19 to 90 years in telephone interviews conducted in three collection phases. Phases 1 and 2 were independent samples, but Phase 3 targeted families of smokers and drinkers from the Phase 1 and 2 samples. The stability of dependence symptoms and consumption was examined for 1158 individuals interviewed in both Phases 1 and 3 (mean interval = 11.0 years). For 1818 individuals interviewed in Phases 2 and 3 (mean interval = 5.5 years) the stability of consumption was examined. Heritability was examined for each collection phase and retest samples from the selected Phase 3 collection. The measures examined were a dependence score, based on DSM-IIIR and DSM-IV criteria for substance dependence, and a quantity × frequency measure. Measures were moderately stable, with test–retest correlations ranging from .58 to .61 for dependence and from .55 to .64 for consumption. However, the pattern of changes over time for dependence suggested that the measure may more strongly reflect recent than lifetime experience. Similar to previous findings, heritabilities ranged from .42 to .51 for dependence and from .31 to .51 for consumption. Consumption was significantly less heritable in the younger Phase 2 cohort (23–39 years) compared to the older Phase 1 cohort (28–90 years).
Major Depression and the Metabolic Syndrome
- Debra L. Foley, Katherine I. Morley, Pamela A. F. Madden, Andrew C. Heath, John B. Whitfield, Nicholas G. Martin
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- Journal:
- Twin Research and Human Genetics / Volume 13 / Issue 4 / 01 August 2010
- Published online by Cambridge University Press:
- 21 February 2012, pp. 347-358
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The aim of this study is to characterize the relationship between major depression and the metabolic syndrome in a large community based sample of Australian men and women aged 26–90 years. A lifetime history of major depression was assessed by telephone interview following the DSM–III-R. A current history of metabolic syndrome was assessed following the United States National Cholesterol Education Program Adult Treatment Panel III (NCEP AP-III) guidelines 1 to 3 years later. Logistic regression was used to estimate the association between depression and the metabolic syndrome, and its component criteria, controlling for age, sex and alcohol dependence. There was no association between a lifetime history of major depression and the presence of the metabolic syndrome. There was a weak association between depression and low high-density lipoprotein cholesterol but not with other component criteria of the metabolic syndrome. Despite calls for interventions directed at depression to reduce the onset of the metabolic syndrome there are important failures to replicate in large samples such as this, no consensus regarding the threshold at which depression may pose a significant risk even allowing for heterogeneity across populations, and no consensus regarding confounders that may explain inter-study differences. The absence of any dosage effect of depression on the associated risk for the metabolic syndrome in other unselected samples does not support a direct causal relationship. The call for intervention studies on the basis of the currently published evidence base is unwarranted.
Limitations of DSM-IV Operationalizations of Alcohol Abuse and Dependence in a Sample of Australian Twins
- Michael T. Lynskey, Elliot C. Nelson, Rosalind J. Neuman, Kathleen K. Bucholz, Pamela A. F. Madden, Valerie S. Knopik, Wendy Slutske, John B. Whitfield, Nicholas G. Martin, Andrew C. Heath
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- Journal:
- Twin Research and Human Genetics / Volume 8 / Issue 6 / 01 December 2005
- Published online by Cambridge University Press:
- 21 February 2012, pp. 574-584
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Alcohol abuse and dependence are among the most common psychiatric conditions identified in epidemiological surveys of the general population. The aim of this article is to examine the psychometric properties of Diagnostic and Statistical Manual of Mental Disorders, (4th ed.; DSM-IV; American Psychiatric Association, 1994) criteria for alcohol abuse and dependence using latent class analysis (LCA). Six thousand two hundred and sixty-five young Australian twins (median age 30 years) were interviewed by telephone between 1996 and 2000 using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). DSM-IV symptoms of alcohol abuse and dependence were collected by structured diagnostic interview and analyzed using methods of LCA. LCA revealed a 4-class solution for women that classified individuals according to the severity of their alcohol- related problems: no/few problems (66.5%), heavy drinking (23.9%), moderate dependence (7.6%) and severe dependence (2.0%). Among men the preferred solution included 5 classes corresponding to no/few problems (46.4%), heavy drinking (34.3%), moderate dependence (12.2%), severe dependence (3.0%) and abuse (4.0%). Evidence of a male-specific class of alcohol-related problems corresponding to abuse partially supports the DSM conceptualization of alcohol use disorders but suggests that this conceptualization — and measurement — may need to be refined for women. Identification of a male- specific abuse class also has important implications for interventions and treatment as these individuals experienced significant alcohol-related problems and comprised approximately 21% of all men classified with an alcohol use disorder.
Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors
- VALERIE S. KNOPIK, ANDREW C. HEATH, PAMELA A. F. MADDEN, KATHLEEN K. BUCHOLZ, WENDY S. SLUTSKE, ELLIOT C. NELSON, DIXIE STATHAM, JOHN B. WHITFIELD, NICHOLAS G. MARTIN
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- Journal:
- Psychological Medicine / Volume 34 / Issue 8 / November 2004
- Published online by Cambridge University Press:
- 04 November 2004, pp. 1519-1530
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Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk.
Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk.
Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47% (95% CI 28–55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0% (95% CI 0–14) to shared environmental factors, and 53% (95% CI 45–63) to non-shared environmental influences.
Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.
022. Endotracheal Intubation Field Experience: Is there a Minimum Amount Required for Paramedics to Maintain Proficiency?
- Robert E. O'Connor, Elsburgh O. Clarke, Dean R. Dobbert, John F. Madden, Ross E. Megargel
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- Prehospital and Disaster Medicine / Volume 10 / Issue S3 / December 1995
- Published online by Cambridge University Press:
- 28 June 2012, p. S51
- Print publication:
- December 1995
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