Biomedical subjects

William G Iacono

Publications and source records attributed to William G Iacono.

At least 19 recordsLinked to original sources

PubMed2025

An Updated Polygenic Index Repository: Expanded Phenotypes, New Cohorts, and Improved Causal Inference.

Polygenic indexes (PGIs) - DNA-based predictors of individual phenotypes - have become essential tools across biomedical and social sciences. We introduce Version 2 of the Polygenic Index Repository, which expands phenotype coverage from 47 to 61, increases the number of participating datasets from 11 to 20, and adopts a more consistent and improved methodology for PGI construction. For 16 phenotypes, we leverage summary statistics from an updated GWAS meta-analysis with greater statistical power compared to the original release, thereby improving the PGI's predictive power. To improve power for family-based analyses, we provide imputed parental PGIs in all datasets with first-degree relatives and offer a framework for interpreting results from analyses that control for parental PGIs. We illustrate the utility of parental PGIs using two applications: (1) comparing PGI associations with and without parental PGI controls for all phenotypes in two Repository datasets with family data, and (2) for BMI and diastolic blood pressure, exploring the contribution of causal versus non-causal components of PGI associations to the imperfect portability of PGIs across subgroups within a genetic ancestry. Collectively, the updates enhance predictive performance, broaden the Repository's scope, and introduce novel resources that reduce confounding bias and improve interpretability.

Journal Article↗

PubMed2007

Longitudinal associations between externalizing behavior and dysfunctional eating attitudes and behaviors: a community-based study.

This study investigated longitudinal associations between externalizing behavior and dysfunctional eating attitudes and behaviors. Participants were girls drawn from the community-based Minnesota Twin Family Study and assessed at ages 11, 14, and 17. Cross-sectional correlations indicated that the strength of the associations between externalizing behavior and dysfunctional eating attitudes and behaviors increased over time. Mixed-model analyses indicated that earlier externalizing behavior predicted increases in weight preoccupation, body dissatisfaction, and use of inappropriate compensatory behaviors. Earlier use of inappropriate compensatory behaviors predicted increases in externalizing behavior.

Adolescent↗

PubMed2006

Personality trait differences in boys and girls with clinical or sub-clinical diagnoses of conduct disorder versus antisocial personality disorder.

This study tested differences in personality traits measured by the Multidimensional Personality Questionnaire (MPQ) in a community sample of adolescents with definite or probable conduct disorder (CD) diagnoses that did not progress to a diagnosis of antisocial personality disorder (ASPD) by early adulthood (n=43), those with definite or probable ASPD that persisted into early adulthood (n=68), or controls with neither a CD nor an ASPD diagnosis (n=716) to examine whether antisocial behaviour disorders that differed in course were associated with differences in personality traits. As expected, boys and girls with ASPD were significantly different from controls on constraint, and those with ASPD were significantly lower on constraint than those with only CD. The results suggest that individual differences in certain personality traits may contribute to differences in the type of antisocial behaviour disorder that emerges and thereby to the course of antisocial behaviour.

Adolescent↗

PubMed2006

The different origins of stability and change in antisocial personality disorder symptoms.

BACKGROUND: Although adult antisocial personality disorder is generally preceded by a pattern of childhood/adolescent conduct problems, only a subset of those who manifest these developmental precursors go on exhibit significant antisocial behavior in adulthood. To date, however, researchers have yet to resolve the origins of either stability or change in antisocial behavior from childhood/adolescence to adulthood. METHOD: The present study sought to fill this gap in the literature, making use of a sample of 626 twin pairs from the ongoing Minnesota Twin Family Study (MTFS). Participants were assessed three times between late adolescence and early adulthood. We made use of biometric Cholesky decomposition and latent growth curve modeling techniques, which allow researchers to disambiguate processes of stability and change and evaluate their respective etiologies (i.e. genetic or environmental). RESULTS: Our results revealed that genetic forces were largely responsible for the stability of adult symptoms of antisocial behavior (AAB) from late adolescence through mid-adulthood, while non-shared environmental influences were primarily responsible for change. Importantly, however, although some of the latter represented systematic and long-lasting influence, much of this non-shared environmental variance appeared transient and idiosyncratic. CONCLUSIONS: Such findings highlight the enduring impact of genetic influences on AAB, and offer insights into the nature of non-shared environmental influences on development.

Adolescent↗

PubMed2006

Decomposing delta, theta, and alpha time-frequency ERP activity from a visual oddball task using PCA.

OBJECTIVE: Time-frequency (TF) analysis has become an important tool for assessing electrical and magnetic brain activity from event-related paradigms. In electrical potential data, theta and delta activities have been shown to underlie P300 activity, and alpha has been shown to be inhibited during P300 activity. Measures of delta, theta, and alpha activity are commonly taken from TF surfaces. However, methods for extracting relevant activity do not commonly go beyond taking means of windows on the surface, analogous to measuring activity within a defined P300 window in time-only signal representations. The current objective was to use a data driven method to derive relevant TF components from event-related potential data from a large number of participants in an oddball paradigm. METHODS: A recently developed PCA approach was employed to extract TF components [Bernat, E. M., Williams, W. J., and Gehring, W. J. (2005). Decomposing ERP time-frequency energy using PCA. Clin Neurophysiol, 116(6), 1314-1334] from an ERP dataset of 2068 17 year olds (979 males). TF activity was taken from both individual trials and condition averages. Activity including frequencies ranging from 0 to 14 Hz and time ranging from stimulus onset to 1312.5 ms were decomposed. RESULTS: A coordinated set of time-frequency events was apparent across the decompositions. Similar TF components representing earlier theta followed by delta were extracted from both individual trials and averaged data. Alpha activity, as predicted, was apparent only when time-frequency surfaces were generated from trial level data, and was characterized by a reduction during the P300. CONCLUSIONS: Theta, delta, and alpha activities were extracted with predictable time-courses. Notably, this approach was effective at characterizing data from a single-electrode. Finally, decomposition of TF data generated from individual trials and condition averages produced similar results, but with predictable differences. Specifically, trial level data evidenced more and more varied theta measures, and accounted for less overall variance.

Adolescent↗

PubMed2006

Using the brain P300 response to identify novel phenotypes reflecting genetic vulnerability for adolescent substance misuse.

We used a novel approach to identify candidate alternative phenotypes for investigating genetic influence underlying substance use disorders (SUDs) in adolescents. The existing literature suggests that P300 amplitude reduction (P3-AR) observed in brain event-related potentials is associated with risk for SUDs generally, not just alcoholism. Using data from a community-based sample of 17-year-old male and female twins, we fit biometric models to P3 amplitude data to show that it is strongly heritable, especially in boys. The extant evidence coupled with our findings strongly supports treating P3-AR as an endophenotype indexing SUD risk. We then examined a set of 15 potential alternative phenotypes (e.g., frequent use of cannabis) to determine whether they were associated with P3-AR. The results indicated that almost all of these alternative phenotypes were associated with P3-AR, with larger effect sizes observed for boys. Given the strong association of these use phenotypes with P3-AR, which is itself an index of genetic risk for SUDs, we conclude that these use phenotypes may provide tools for finding vulnerability genes in adolescents who have yet to pass through the age of risk for SUDs.

Adolescent↗

PubMed2006

The association of early adolescent problem behavior and adult psychopathology: a multivariate behavioral genetic perspective.

Research has documented a strong association between early adolescent problem behavior and adult disinhibitory psychopathology, leading some to suggest that the latter can be reduced by preventing or delaying the former. But the prevention implications of this association necessarily depend upon the causal mechanisms that produce it. The current study was designed to test implications of a model that posits that early problem behavior and disinhibitory psychopathology are associated because they are both manifestations of a common inherited liability. At their age-17 assessment, 1080 twins from the older cohort of the Minnesota Twin Family Study reported whether and the age at which they first: drank alcohol, used tobacco, used illicit drugs, had sexual intercourse, and had police contact. An Early Problem Behavior index was computed by summing the number of these experiences each participant reported having before age 15. Outcome measures of disinhibitory psychopathology were assessed by clinical interview at the age-20 follow-up and included number of symptoms of nicotine dependence, alcohol abuse and dependence, drug abuse and dependence, and adult antisocial behavior. Biometric analysis of the multivariate twin data showed that: (1) early adolescent problem behavior is weakly heritable (approximately 20%), (2) the common factor underlying disinhibitory psychopathology is strongly heritable (approximately 75%), and (3) the phenotypic correlation between early adolescent problem behavior and disinhibitory psychopathology was strong (approximately 0.60) and accounted for primarily by genetic factors common to the two domains. Findings are discussed in the context of research on the prevention and developmental nature of substance use disorders and related psychopathology.

Adolescent↗

PubMed2006

Timing of menarche and the origins of conduct disorder.

CONTEXT: Precocious onset of menses (ie, age < or =11 years) has repeatedly been identified as a risk factor for higher rates of delinquency or conduct disorder (CD) in girls. Although this association is often conceptualized as environmentally mediated (via processes such as affiliation of early-menstruating youth with older, more deviant peers), such conclusions are premature as biological and genetic explanations have yet to be fully considered. OBJECTIVE: To uncover the origins of the association between CD and timing of menarche. DESIGN, SETTING, AND PARTICIPANTS: The sample consisted of a population-based birth cohort of 708 mid-adolescent female twins assessed as part of the ongoing Minnesota Twin Family Study. We conducted 2 sets of analyses: standard bivariate analyses to uncover possible common genes and moderator analyses to evaluate possible moderation of genetic influences on CD by timing of menarche. MAIN OUTCOME MEASURES: Conduct disorder was assessed via individual semistructured interviews with mothers and adolescents. Menarcheal status and age at menarche were assessed via the Pubertal Development Scale. RESULTS: The results argued against common genetic influences but did provide evidence of etiological moderation of CD by timing of menarche. The heritability of CD was strongest (67%) in girls with average timing of menarche (ie, age 12-13 years) and substantially weaker (8%) in those with early onset. Those with late initiation of menses (ie, age >13 years) similarly exhibited weaker genetic influences (29%). Shared environmental influences showed the opposite pattern, as they were far stronger for those with precocious and delayed onset vs those with average onset. CONCLUSIONS: Our findings provide indirect support for psychosocial interpretations of the impact of precocious menarche and, to a lesser extent, delayed menarche on CD development. Further, they lend support to the notion that in some cases, genetic influences on psychopathology may be strongest in the "average, expectable" environment.

Age Factors↗

PubMed2006

Beyond the DSM: defining endophenotypes for genetic studies of substance abuse.

Although substance-related disorders are heritable, the genetic factors contributing to vulnerability to these disorders are expected to be complex. Nonetheless, identifying genes underlying this vulnerability and understanding their relationship with environmental factors and behavior holds the promise of dramatic advances in diagnosis, prevention, and treatment. The search is complicated by a number of factors, however, including the weak validity of psychiatric diagnosis for identifying gene carriers, the complexity of the brain and behavior, and the numerous intervening variables between genetic transcription and its behavioral consequences. One strategy for bridging this theoretical gap is to study endophenotypes--biologic correlates of disorders that precede their overt development, may have higher reliability than behavioral measures, and present simpler relationships with a smaller number of genes. This article reviews research suggesting the usefulness of several putative endophenotypes for substance-related disorders, including 1) reduced P3 amplitude of the visual event-related potential, 2) increased EEG beta power, 3) a lowered level of response to an alcohol challenge, and 4) the inability to modulate autonomic nervous system reactivity under the stress of anticipating a predictable aversive stimulus.

Brain↗

PubMed2006

Genetic and environmental influences on academic achievement trajectories during adolescence.

Most studies have considered the effects of particular characteristics on academic achievement individually, which means that little is known about how they function together. Using the population-based Minnesota Twin Family Study, the authors investigated the effects of child academic engagement (interest, involvement, effort), IQ, depression, externalizing behavior, and family environmental risk on academic achievement (reported school grades) from ages 11 through 17. Hierarchical linear growth curve modeling showed main effects on initial reported Grades for all variables, and IQ mitigated the deleterious effects of family risk and externalizing. Only engagement affected change in Grades through adolescence. Influences on initial Grades were strongly genetically influenced, associated primarily with IQ, engagement, and externalizing behavior. Shared environmental influences on initial Grades linked engagement, IQ, and family risk. Genetic influences on change in Grades were substantial, but they were not associated with the academic, family risk, and mental health covarying factors. These results indicate that age 11 achievement and change in achievement through adolescence show systematic patterns and document the existence of individual differences in the commonly shared developmental experience of adapting to the school environment.

Achievement↗

PubMed2006

Differential parent-child relationships and adolescent externalizing symptoms: cross-lagged analyses within a monozygotic twin differences design.

Research has indicated that differential parental treatment is linked to differences in externalizing symptomology (EXT) across siblings, even those siblings who are genetically identical. However, the direction of causation and longitudinal significance of this relationship remains unclear. Thus, in the present study, the authors examined 486 monozygotic twin pairs, assessed at ages 11, 14, and 17 years, within a cross-lagged twin differences design. Results revealed that differential parent-child conflict at age 11 years uniquely contributed to differential sibling EXT 3 years later but only in the most discordant twin pairs. In the full, unselected sample, this relationship was not significant. These results suggest that markedly different parent-child conflict has an environmentally mediated impact on child behavior through mid-adolescence, findings that yield insights into environmental influences on behavior.

Adolescent↗

PubMed2006

Personality traits and the development of nicotine, alcohol, and illicit drug disorders: prospective links from adolescence to young adulthood.

The personality traits constraint (CN) and negative emotionality (NE) have been more (CN) or less (NE) consistently associated with alcoholism. The authors examined the association of personality at age 17 with timing of onset and with prospective prediction of nicotine, alcohol, and illicit drug disorders 3 years later in a twin sample (569 females; 432 males). Earlier onset of alcohol and drug disorders (by age 17) was related to significantly lower CN compared with later onsets (by age 20); high NE was related to either onset. NE, as well as CN, uniquely predicted new onsets of all 3 types of substance use disorders by follow-up, with preexisting substance disorders taken into account. Personality traits confer generalized risk for developing any substance disorder, though some traits are more strongly linked with some substance disorders than with others.

Adolescent↗

PubMed2006

Continuity and change in psychopathic traits as measured via normal-range personality: a longitudinal-biometric study.

The discriminant validity of the interpersonal-affective and social deviance traits of psychopathy has been well documented. However, few studies have explored whether these traits follow distinct or comparable developmental paths. The present study used the Multidimensional Personality Questionnaire (A. Tellegen, in press) to examine the development of the psychopathic traits of Fearless Dominance (i.e., interpersonal-affective) and Impulsive Antisociality (i.e., social deviance) from late adolescence to early adulthood in a longitudinal-epidemiological sample of male and female twins. Results from mean- and individual-level analyses revealed stability in Fearless Dominance from late adolescence to early adulthood, whereas Impulsive Antisociality declined over this developmental period. In addition, biometric findings indicated greater genetic contributions to stability in these traits and greater nonshared environmental contributions to their change over time. Collectively, these findings suggest distinct developmental trends for psychopathic traits from late adolescence to early adulthood.

Adolescent↗

PubMed2006

Personality differences in children and adolescents with attention-deficit/hyperactivity disorder, conduct disorder, and controls.

BACKGROUND: Differences in personality profiles were examined between children who differed in their co-morbidity of externalizing disorders: attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). METHODS: 11- and 17-year-old male and female twins from a community sample were categorized as ADHD only, CD only, co-morbid CD-ADHD, and controls (no ADHD or CD) based on threshold and subthreshold CD and ADHD diagnoses assessed with structured interviews. Multivariate analyses were used to identify patterns of personality that differentiate these four diagnostic groups. It was hypothesized that significant differences would be found in the pattern of personality variables between participants in the co-morbid group, compared to the other three groups, and that these differences would hold across developmental periods. RESULTS: As expected, the co-morbid group had a pattern of personality marked by higher Negative Emotionality and lower Constraint than the other diagnostic groups. This pattern was evidenced across gender and age cohort. CONCLUSIONS: An extreme personality profile may represent a liability toward the occurrence of ADHD and CD with more extreme profiles contributing to the occurrence of both disorders among boys and girls. Implications for treatment planning and theoretical development are discussed.

Adolescent↗

PubMed2006

P300 amplitude as an indicator of externalizing in adolescent males.

Reduced P300 amplitude is reliably found in individuals with a personal or family history of alcohol problems. However, alcoholism is part of a broader externalizing spectrum that includes other substance use and antisocial disorders. We hypothesized that reduced P300 is an indicator of the common factor that underlies disorders within this spectrum. Community males (N=969) were assessed at age 17 in a visual oddball task. Externalizing was defined as the common factor underlying symptoms of alcohol dependence, drug dependence, nicotine dependence, conduct disorder, and adult antisocial behavior. A robust association was found between reduced P300 amplitude and the externalizing factor, and this relation accounted for links between specific externalizing disorders and P300. Our findings indicate that reduced P300 amplitude is an indicator of the broad neurobiological vulnerability that underlies disorders within the externalizing spectrum.

Adolescent↗

PubMed2006

Association between P3 event-related brain potential amplitude and adolescent problem behavior.

This study examined P3 event-related brain potential amplitude and the age of onset of adolescent problem behaviors associated with the development of externalizing psychopathology. Five hundred and one male and 627 female 17-year-old twins reported whether and when they had initiated tobacco, alcohol, or illicit drug use, had police contact, or had sexual intercourse. P3 amplitude was recorded using a visual oddball task. Each of these behaviors was associated with reduced P3 amplitude. When these five behaviors were used to create a composite early problem behavior scale reflecting onset prior to age 15, higher scores were associated with smaller P3 amplitudes. P3 amplitude reduction has been associated with genetic risk for alcoholism and other externalizing disorders associated with disinhibited behavior. Our results suggest that reduced P3 may also be associated with early expression of behaviors that predict the development of these disorders.

Adolescent↗

PubMed2006

Heritability of P300 amplitude development from adolescence to adulthood.

Early adulthood is a period of late brain development corresponding to the age of onset for psychopathology associated with P300 amplitude reductions. Although amplitude from a single occasion is heritable, little is known about genetic influences on change during this period. This is the first study of P300 change to combine latent growth and twin models. P300 at Pz was measured up to three times at approximately ages 17, 20, and 23 in monozygotic and dizygotic male twins using a visual task. P300 decreased with age. Correlations indexing the stability of amplitude over time were high (median r=.72) and almost 90% of the stable variance (i.e., the model intercept) was attributable to genetic influences. The rate of decrease was heritable, and the genes influencing intercept may be the same ones influencing change. Finally, intercept was more heritable than amplitude at any single time point. Intercept may be a more useful aid in the search for genes associated with relevant psychopathology than single measures of P300. Over a broader age range growth indices may be useful "developmental" endophenotypes.

Adolescent↗

PubMed2005

The Minnesota Eating Behavior Survey: a brief measure of disordered eating attitudes and behaviors.

This article describes details of the development and psychometric characteristics of a brief self-report inventory for assessing attitudes and behaviors symptomatic of eating disorders that is currently in use in a longitudinal study of over 700 families with 11-year-old or 17-year-old twin girls. The Minnesota Eating Behavior Survey (MEBS), formerly the Minnesota Eating Disorder Inventory, is a 30-item measure developed for use with children as young as 10 years as well as adults. An examination of the MEBS's psychometric properties in a large, community sample of girls, women, and men demonstrated good factor congruence, internal consistency reliability, three-year stability, as well as evidence of concurrent and criterion validity. This questionnaire has promise as a screening and assessment measure for eating disturbance in cross-sectional and longitudinal research involving individuals of a wide range of ages.

Adolescent↗