Genetic Research: Who Is At Risk for Alcoholism? by ProQuest

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									                                     Genetic Research

                                Who Is At Risk for Alcoholism?
              Tatiana Foroud, Ph.D.; Howard J. Edenberg, Ph.D.; and John C. Crabbe, Ph.D.

          The National Institute on Alcohol Abuse and Alcoholism (NIAAA) was founded 40 years ago to help
          elucidate the biological underpinnings of alcohol dependence, including the potential contribution of
          genetic factors. Twin, adoption, and family studies conclusively demonstrated that genetic factors
          account for 50 to 60 percent of the variance in risk for developing alcoholism. Case–control studies
          and linkage analyses have helped identify DNA variants that contribute to increased risk, and the
          NIAAA­sponsored Collaborative Studies on Genetics of Alcoholism (COGA) has the expressed goal of
          identifying contributing genes using state­of­the­art genetic technologies. These efforts have
          ascertained several genes that may contribute to an increased risk of alcoholism, including certain
          variants encoding alcohol­metabolizing enzymes and neurotransmitter receptors. Genome­wide
          association studies allowing the analysis of millions of genetic markers located throughout the genome
          will enable discovery of further candidate genes. In addition to these human studies, genetic animal
          models of alcohol’s effects and alcohol use have greatly advanced our understanding of the genetic
          basis of alcoholism, resulting in the identification of quantitative trait loci and allowing for targeted
          manipulation of candidate genes. Novel research approaches—for example, into epigenetic
          mechanisms of gene regulation—also are under way and undoubtedly will further clarify the genetic
          basis of alcoholism. KEY WORDS: Alcohol dependence; alcoholism; genetics and heredity; genetic theory of alcohol
          and other drug (AOD) use; genetic causes of AOD use, abuse and dependence (genetic AOD); genetic risk and
          protective factors; hereditary versus environmental factors; genetic mapping; Collaborative Studies on Genetics of
          Alcoholism; human studies; animal studies




                                                 The National Institute on Alcohol

E
       vidence from archeological artifacts
                                              Abuse and Alcoholism (NIAAA)                                   TATIANA FOROUD, PH.D., is a
       indicates that fermented beverages
                                              was founded 40 years ago to further                            Chancellor’s Professor in the Department
       existed as early as 10,000 B.C.                                                                       of Medical and Molecular Genetics,
The excessive consumption of alcohol,         understanding of the biological
                                              underpinnings of alcohol dependence.                           Indiana University School of Medicine,
however, results in dangers to the                                                                           Indianapolis, Indiana.
health and well being of the drinker          Early genetic studies were focused
and those around him or her. Today,           on delineating whether environmental
                                              factors, genetic factors, or both con­                         HOWARD J. EDENBERG, PH.D., is a
the World Health Organization estimates                                                                      Distinguished Professor in the Department
that alcohol causes 1.8 million deaths        tributed to the risk for alcohol depen­
                                              dence. Once it was apparent that                               of Biochemistry and Molecular Biology
(3.2 percent of all deaths) worldwide                                                                        and the Department of Medical and
and 58.3 million (4 percent of total)         genetics did indeed play a role in alcohol
                                              dependence, NIAAA began to fund                                Molecular Genetics, both at the Indiana
disability­adjusted life­years (DALYs)1                                                                      University School of Medicine,
lost to disease (http://www.who.int/          studies seeking to identify relevant
                                                                                                             Indianapolis, Indiana.
substance_ abuse/facts/alcohol/en/            genes. Since then, studies in humans
index.html). In the United States, alco­      and animals have used complementary
                                                                                                             JOHN C. CRABBE, PH.D., is a professor
hol dependence (i.e., alcoholism) is a        approaches to understand the genetics
                                                                                                             in the Department of Behavioral
major health problem, affecting 4 to 5        of alcohol use and dependence. This                            Neuroscience, Oregon Health & Science
percent of the population at any given        overview summarizes the evidence                               University, and a senior research career
time, with a lifetime prevalence of 12.5      1
                                               DALYs are a measure of burden of disease. One DALY is equal
                                                                                                             scientist at the VA Medical Center,
percent (Hasin et al. 2007).                  to 1 healthy year of life lost.                                Portland, Oregon.

64                                                                                                                              Alcohol Research & Health
                                                                                            Genetic Research and Risk for Alcoholism


supporting a role for genetic factors        Strategies for Identifying
                      possible to scan the genome using
in alcoholism and describes how new          Genes Contributing to
                           a type of genetic variation called
genetic findings could affect our            Alcohol Dependence
                              microsatellites. In this approach,
understanding of the causes and factors                                                       called linkage analysis, the pattern
contributing to this debilitating disease    Researchers have developed several               of transmission of a disease (e.g.,
and could potentially guide the devel­       strategies to identify genes that contribute     alcoholism) in families with multiple
opment of improved treatments.               to differences in the risk for alcohol           affected members is compared with
                                             dependence, including case–control               the pattern of transmission of certain
                                             studies and linkage analyses. These              microsatellites (see figure 1B). The
                                             strategies depend on the premise that            underlying hypothesis is that alcoholics
Evidence of a Genetic                        for a particular position in the DNA             within a family share many risk alleles;
Contribution to Alcohol                
								
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