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Matt McGue

Publications and source records attributed to Matt McGue.

At least 19 recordsLinked to original sources
PubMed2026

Robust inference and correlates from genetic associations with personality.

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustness, their generalizability and the biological and social pathways through which they act. Here we meta-analyse data across 46 cohorts comprising 611,037 to 1.14 million participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism and openness to experience), and data from up to 50,725 participants for within-family GWAS. We identify 1,260 lead genetic variants associated with personality, including 824 novel variants3. Common genetic variants explain a moderate 4.8-9.3% of the variance in measures of each trait, and 9.3-13.3% among instruments with typical measurement reliability. Genetic associations with personality are highly consistent but not identical across geography, reporter (self versus close other), age group and measurement instrument, and we find minimal spousal assortment for personality in recent history. In contrast to many other social and behavioural traits4,5, within-family GWAS and polygenic index analyses indicate that genetic associations with personality are minimally confounded by the shared family environment. Polygenic prediction, genetic correlation and Mendelian randomization analyses indicate that personality traits have widespread, potentially causal associations with consequential behaviours and life outcomes. Overall, we find that the genetic architecture of personality is robustly generalizable, minimally confounded and widely relevant to human experience.

Journal Article↗
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↗
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

Comparison of academic performance of twins and singletons in adolescence: follow-up study.

OBJECTIVES: To determine whether twins in recent cohorts show similar academic performance in adolescence to singletons and to test the effect of birth weight on academic performance in twins and singletons. DESIGN: Follow-up study. SETTING: Denmark. PARTICIPANTS: All twins (n=3411) and a 5% random sample of singletons (n=7796) born in Denmark during 1986-8. MAIN OUTCOME MEASURES: Test scores in ninth grade (age 15 or 16), birth weight, gestational age at birth, parents' age, and parents' education. RESULTS: Ninth grade test scores were normally distributed, with almost identical mean and standard deviations for twins and singletons (8.02 v 8.02 and 1.05 v 1.06) despite the twins weighing on average 908 g (95% confidence interval 886 to 930 g) less than the singletons at birth. Controlling for birth weight, gestational age at birth, age at test, and parents' age and education confirmed the similarity of test scores for twins and singletons (difference 0.04, 95% confidence interval -0.03 to 0.10). A significant, positive association between test score and birth weight was observed in both twins and singletons, but the size of the effect was small: 0.06-0.12 standard deviations for every kilogram increase in birth weight. CONCLUSIONS: Although older cohorts of twins have been found to have lower mean IQ scores than singletons, twins in recent Danish cohorts show similar academic performance in adolescence to that of singletons. Birth weight has a minimal effect on academic performance in recent cohorts; for twins this effect is best judged relative to what is a normal birth weight for twins and not for singletons.

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

Genetic influence on human lifespan and longevity.

There is an intense search for longevity genes in both animal models and humans. Human family studies have indicated that a modest amount of the overall variation in adult lifespan (approximately 20-30%) is accounted for by genetic factors. But it is not known if genetic factors become increasingly important for survival at the oldest ages. We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. Mean lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)] years for every year his co-twin survives past age 60 years. This rate is significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ) males. Females and males have similar rates and these are negligible before age 60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to old ages substantially and significantly increases the chance of reaching the same old age and this chance is higher for MZ than for DZ twins. The relative recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for females and males are very similar, but with a shift of the female pattern with age that corresponds to the better female survival. Similar results arise when considering only those Nordic twins that survived past 75 years of age. The present large population based study shows genetic influence on human lifespan. While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages.

Adolescent↗
PubMed2006

Age trajectories of grip strength: cross-sectional and longitudinal data among 8,342 Danes aged 46 to 102.

PURPOSE: The purpose is to study the age trajectory of hand-grip strength after the age of 45 years. METHODS: In this study, we use data from three large nationwide population-based surveys of Danes aged 45 to 102 years with a total of 8342 participants with grip-strength measurements and up to 4 years of follow-up. Grip strength was measured by using a portable hand dynamometer. RESULTS: Grip strength declines throughout life for both males and females, but among the oldest women, the longitudinal curve reaches a horizontal plateau. The course of the decline is estimated by using full information in the longitudinal data and is found to be almost linear in the age span of 50 to 85 years. In this age span, mean annual grip-strength loss is estimated to be 0.59 (0.02) (SE) kg for men and 0.31 (0.01) kg for women. CONCLUSION: This study confirms the previously reported grip-strength decline with increasing age. Estimates were obtained by using full-information methods from large population-representative studies. Equations of expected grip strength, as well as tables with sex-, age-, and height-stratified reference data, provide an opportunity to include grip-strength measurement in clinical care in similar populations.

Aged↗
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

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

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

Apolipoprotein e genotypes: relationship to cognitive functioning, cognitive decline, and survival in nonagenarians.

OBJECTIVES: To evaluate the extent to which relationships between apolipoprotein E, cognitive functioning, and survival in people aged 60 to 80 persist into advanced old age. DESIGN: Examine the effect of apolipoprotein E genotypes on baseline cognitive functioning, cognitive decline over 5 years, and survival in a cohort of 1,551 nonagenarians. SETTING: The Danish 1905 birth cohort. PARTICIPANTS: One thousand five hundred fifty-one nonagenarians from the Danish 1905 birth cohort. MEASUREMENTS: Cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and five brief cognitive tests (cognitive composite). RESULTS: The subjects were stratified into four groups by occurrence of a protective (epsilon2) or a risk (epsilon4) apo E allele (epsilon22 and epsilon23, epsilon33, epsilon24 and epsilon34, epsilon44). At intake, the mean scores for the three genotype groups were 22.1, 21.8, 21.4, and 21.0 for MMSE and 0.10, 0.07, -0.02, and 0.30 for the cognitive composite, respectively. Growth-curve analyses showed that, although individuals carrying at least one epsilon4 allele had slightly lower MMSE scores and declined slightly more rapidly over time, this effect was not statistically significant and was not apparent in scores on the cognitive composite. In subjects whose functioning was relatively well preserved (those still living and able to participate in the assessment, and whose cognitive functioning had declined less than 4 points on the MMSE), epsilon4 frequencies tended to decline at subsequent waves (P=.03, chi-square test for trend), but epsilon4 had no significant survival disadvantage (hazard ratio=1.11 (95% confidence interval=0.99-1.25; P=.07). CONCLUSION: Apo E genotype has a small effect on the probability of remaining a well-functioning nonagenarian but no separately detectable effect on cognitive functioning, cognitive decline, or survival.

Aged, 80 and over↗
PubMed2006

Possible associations between successful aging and polymorphic markers in the Werner gene region.

Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by mutations in the Werner (WRN) gene leading to the early onset of many (but not all) aspects of normal aging. To investigate whether the WRN gene affects the course of aging in non-Werner syndrome individuals, we performed association studies analyzing several single nucleotide polymorphisms (SNPs) in the WRN locus. We found certain close-set SNPs in the 5' flanking region and 5' UTR to be significantly associated with the cognitive functioning level in old age.

5' Flanking Region↗