摘要:

AbstractOver the last decade, molecular genetics has become one of the most important technologies in medical research. However, the application of these approaches to neuropsychiatric disorders has been met with both unreasonable expectations, and at times, unreasonable criticism. Molecular genetics has opened a new window into these disorders that has great promise, but is likely to reveal a complex reality. Clearly, the potential exists to actually define some of the disorders that make up the syndromes that we are studying. In doing so, we will not only begin to address the fundamental pathophysiology of these disorders, but also begin to design treatments based on this new understanding. In this report, a series of four papers on the genetics programs of the National Institutes of Health will be introduced. © 1994 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractFor some time it has been known through the results of family, twin, and adoption studies that heredity appears to play a significant causal role in many mental disorders, including schizophrenia, bipolar disorder, and other mood disorders, Alzheimer's Disease, panic disorder, obsessive compulsive disorder, autism, dyslexia, and Tourette's Syndrome. The precise patterns of inheritance of these complex disorders have not been determined, nor have the relevant genes been localized or cloned. Because the genetics are complex and because there is also clearly an environmental contribution to behavior, we expect the analysis of the genetics of mental illness to be arduous, and not quickly resolved. There are several compelling reasons to continue to focus our attention on uncovering the genetic factors for severe mental illness. Prominent among these are the implications for better treatment of mental disorders. The National Institute of Mental Health supports a wide range of studies on psychiatric genetic research. © 1994 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIt is becoming clear that there is a genetic component to drug abuse. Family studies, adoption studies, and critical twin studies have all pointed to some genetic vulnerability or risk factors for an individual to abuse psychoactive drugs depending on certain psychopathologies in the biological parents and/or parents' own drug use. The question for the next generation of research at the National Institute on Drug Abuse (NIDA) is to apply the rapidly developing technology in molecular genetics in an effort to determine the candidate genes contributing to the risk. © 1994 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research to elucidate the specific genetic factors, now largely unknown, which underlie susceptibility to alcoholism and its medical complications (including fetal alcohol syndrome). Because of the genetic complexity and heterogeneity of alcoholism, identification of the multiple underlying factors will require the development of new study designs and methods of analysis of data from human families. While techniques of genetic analysis of animal behavioral traits (e.g., targeted gene disruption, quantitative trait locus (QTL) mapping) are more powerful than those applicable to humans (e.g., linkage and allelic association studies), the validation of animal behaviors as models of aspects of human alcoholism has been problematic. Newly developed methods for mapping QTL influencing animal behavioral traits can not only permit analyses of human family data to be directly informed by the results of animal studies, but can also serve as a novel means of validating animal models of aspects of alcoholism. © 1994 Wiley‐Liss, Inc.This article is a U.S. Government work and, as such, is in the public domain in the United States of Ameri

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe National Institute of Neurological Disorders and Stroke (NINDS) supports research concerning the determinants of normal and pathological development of the nervous system, from the genetic to the environmental. NINDS also funds basic and clinical research concerning the etiology, diagnosis, treatment, consequences, and prevention of the spectrum of neurodevelopmental disorders including neurobehavioral and neurodegenerative disorders (National Advisory Council Neurological Disorders and Stroke, 1989, 1992; Division of Convulsive, Developmental and Neuromuscular Disorders, NINDS, 1993). © 1994 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractRecent analysis of the candidate gene, association study for psychiatric disorders have concluded that most statistically significant results are likely to be false positives because there are a large number of potential candidate loci and a low a priori probability that a given candidate locus will in fact be trait relevant. Hence, it was recommended that the α level (Plevel) be lowered for association studies. The present study demonstrates that lowering the α level to some fixed, predetermined value is not a recommended strategy. Rather, the probability of false positives (and false negatives) depends on such parameters as the prevalence of the disorder, the prevalence of the genotypes at the candidate locus, and the relative risk. In some areas of the parameter space, the adjustment to α may be modest. In other areas, however, even the requirement of one or more independent replications of the original results gives false positive rates exceeding 80% or 90%. Hence, thePlevels required to minimize false positives may have to be changed from one statistical test to another even within the same study. A procedure for adjusting the probability level for a test of association between genotypes and a disorder is given. © 1994 Wiley‐Liss

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractHuman genetics researchers have been intrigued for many years by weak‐to‐moderate associations between markers and diseases. However, in most cases of association, the cause of this phenomenon is still unknown. Recently, interest has grown in pursuing association studies for complex psychiatric diseases, either instead of or in addition to linkage studies. However, it is one thing todetectassociation; the next important step is to determinewhy. Here we consider what a disease‐marker association in the weak‐to‐moderate range (relative risk<5) can tell us about disease etiology. Two distinct models (not the only possibilities) which could explain such an association are formulated. One is a linkage disequilibrium or major disease gene model, involving tight linkage with a “necessary” major gene. The other is a pure association model, involving a “susceptibility” gene that has only a minor effect on disease state. It will be shown that association analysis cannot distinguish between these two models, and hence cannot elucidate the biological mechanism behind the association. (This statement holds for traditional population‐based association tests, as well as for more recent family‐based association tests.) The importance of drawing the distinction between these two genetic models and the implications for understanding the genetics of complex human disease will also be discussed.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractData on unreasonable fears of blood, needles, hospitals, and illness (BNHI) were collected by telephone interview from 541 MZ and 388 DZ pairs of female twins from the population‐based Virginia Twin Registry. BNHI phobia was defined as the presence of fear accompanied by interference. Age at onset of phobia was found to be very similar to that of situational phobias previously assessed in the sample. Using a multiple threshold model, we found no evidence for qualitative differences between BNHI fears and BNHI phobia. The familial aggregation of fears appears to be entirely due to additive genetic variance. The possible exception to this is fear of illness, which, like BNHI phobias, seems to aggregate within families because of shared environmental factors. Although power to discriminate between the causes of familial resemblance is low, results suggest that random traumatic events and some social learning may be responsible for the onset of BNHI phobias. About two‐thirds of variance is individual‐specific environmental, and could include genotype x environment interaction and measurement error. © 1994 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY