Gene-environment interaction in expertise acquisition: Practice effects on musical expertise vary by polygenic scores for cognitive performance.

Expert performance is associated with practice, partly because of causal effects of practice on skill (i.e., learning). However, the practice-expertise association is also influenced by a complex interplay between genes and environment including partly overlapping genetic influences. The importance of cognitive ability in the practice-expertise association is less well understood. Therefore, we first examined whether genetic predisposition for cognitive performance, operationalized as a polygenic score, is associated with music practice and expertise. Next, we tested whether there is evidence for gene × environment interaction, i.e., whether effects of practice on expertise differ depending on an individual's genetic predisposition for cognitive performance. Polygenic scores for cognitive performance (PGScp) and multi-trait cognitive performances, including educational attainment and mathematical performances (PGScps) were calculated for approximately 3800 genotyped Swedish individuals with information available on their cumulative amount of music practice, musical achievement, and musical auditory discrimination. We found that higher PGScp and PGScps were associated with higher levels of achievement, musical auditory discrimination, and more practice, although the association with practice weakened when controlling for education. Music practice was linked to both expertise outcomes, and the effect sizes of these associations varied depending on an individual's PGScp and PGScps (with the exception of PGScp for musical auditory discrimination). These results suggest genetic pleiotropy between cognitive performance and musical expertise. Additionally, they reveal the presence of G × E interaction in skill acquisition, as effects of practice on musical expertise are stronger for individuals with a higher genetic predisposition for cognitive performance.

Nuanced HEXACO: A Meta-Analysis of HEXACO Cross-Rater Agreement, Heritability, and Rank-Order Stability.

Most Five-Factor Model (FFM) questionnaire items contain unique variance that is partly heritable, stable, and consensually observable, demonstrates consistent associations with age and sex, and predicts life outcomes beyond higher order factors. Extending these findings to the HEXACO model, we meta-analyzed single-item cross-rater agreement, heritability, and 2-year stability using samples from six countries. We analyzed raw item scores and their residual variance and adjusted the estimates for measurement unreliability. The median cross-rater agreement, heritability, and stability estimates were, respectively, .30, .30, and .57, for raw items and .10, .16, and .39, for item residuals. Adjusted for reliability, the respective medians were .46 and .25 for cross-rater agreement, .46 and .39 for heritability, and .87 and .94 for stability. These results are strikingly consistent with FFM-based findings, providing nondismissible evidence that single items index a partly unique level of the trait hierarchy-personality nuances-with trait properties comparable to those of higher-order traits.

Notes from Beethoven's genome.

Rapid advances over the last decade in DNA sequencing and statistical genetics enable us to investigate the genomic makeup of individuals throughout history. In a recent notable study, Begg et al.1 used Ludwig van Beethoven's hair strands for genome sequencing and explored genetic predispositions for some of his documented medical issues. Given that it was arguably Beethoven's skills as a musician and composer that made him an iconic figure in Western culture, we here extend the approach and apply it to musicality. We use this as an example to illustrate the broader challenges of individual-level genetic predictions.

Can flow proneness be protective against mental and cardiovascular health problems? A genetically informed prospective cohort study.

Flow is a phenomenon where one experiences optimal challenge, marked by an intense, effortless, and rewarding concentration on a task. Past research shows that flow proneness is associated with good mental and cardiovascular health. However, this research has been primarily cross-sectional, based on self-report data, and has not controlled for potential confounding effects of neuroticism. In a large, longitudinal twin sample (N = 9361), we used nationwide patient registry data to test whether flow proneness predicted registry-based diagnoses of depression, anxiety, schizophrenia, bipolar disorder, stress-related disorders, or cardiovascular diseases. We used survival analyses taking time to diagnosis into account to test if (a) there is a relationship between flow proneness and health diagnoses over time, (b) neuroticism confounds this relationship, and (c) the relationship remains present within discordant monozygotic twin pairs (N = 952), thereby controlling for genetic and shared environmental confounding. Individuals with higher flow proneness had a decreased risk of receiving diagnoses for depression (16%; CI [14%, 18%]), anxiety (16%; CI [13%, 18%]), schizophrenia (15%; CI [4%, 25%]), bipolar (12%; CI [6%, 18%]), stress-related (9%; CI [9%, 12%]), and cardiovascular disorders (4%; CI [1%, 8%]). When controlling for neuroticism, higher flow proneness still decreased the risk of depression (6%; CI [3%, 9%]) and anxiety diagnoses (5%; CI [1%, 8%]). Monozygotic twins who experienced more flow than their co-twin had a lower risk for depression (16%; CI [5%, 26%]) and anxiety (13%; CI [1%, 24%]), though only the association with depression remained significant when also controlling for neuroticism (13%; CI [1%, 24%]). Findings are in line with a causal protective role of flow experiences on depression and potentially anxiety and highlight that neuroticism and familial factors are notable confounding factors in observed associations between flow proneness and health outcomes.

Adolescent Psychedelic Use and Psychotic or Manic Symptoms.

Importance: While psychedelic-assisted therapy has shown promise in the treatment of certain psychiatric disorders, little is known about the potential risk of psychotic or manic symptoms following naturalistic psychedelic use, especially among adolescents. Objective: To investigate associations between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents using a genetically informative design. Design, Setting, and Participants: This study included a large sample of adolescent twins (assessed at age 15, 18, and 24 years) born between July 1992 and December 2005 from the Swedish Twin Registry and cross-sectionally evaluated the associations between past psychedelic use and psychotic or manic symptoms at age 15 years. Individuals were included if they answered questions related to past use of psychedelics. Data were analyzed from October 2022 to November 2023. Main Outcomes and Measures: Primary outcome measures were self-reported psychotic and manic symptoms at age 15 years. Lifetime use of psychedelics and other drugs was also assessed at the same time point. Results: Among the 16 255 participants included in the analyses, 8889 were female and 7366 were male. Among them, 541 participants reported past use of psychedelics, most of whom (535 of 541 [99%]) also reported past use of other drugs (ie, cannabis, stimulants, sedatives, opioids, inhalants, or performance enhancers). When adjusting for substance-specific and substance-aggregated drug use, psychedelic use was associated with reduced psychotic symptoms in both linear regression analyses (ß, -0.79; 95% CI, -1.18 to -0.41 and ß, -0.39; 95% CI, -0.50 to -0.27, respectively) and co-twin control analyses (ß, -0.89; 95% CI, -1.61 to -0.16 and ß, -0.24; 95% CI, -0.48 to -0.01, respectively). In relation to manic symptoms, likewise adjusting for substance-specific and substance-aggregated drug use, statistically significant interactions were found between psychedelic use and genetic vulnerability to schizophrenia (ß, 0.17; 95% CI, 0.01 to 0.32 and ß, 0.17; 95% CI, 0.02 to 0.32, respectively) or bipolar I disorder (ß, 0.20; 95% CI, 0.04 to 0.36 and ß, 0.17; 95% CI, 0.01 to 0.33, respectively). Conclusions and Relevance: The findings in this study suggest that, after adjusting for other drug use, naturalistic use of psychedelic may be associated with lower rates of psychotic symptoms among adolescents. At the same time, the association between psychedelic use and manic symptoms seems to be associated with genetic vulnerability to schizophrenia or bipolar I disorder. These findings should be considered in light of the study's limitations and should therefore be interpreted with caution.

Heritability of adult picky eating in the Netherlands.

Adult picky eating (APE), the rejection of familiar and unfamiliar foods leading to a diet with limited variety, is an understudied phenomenon which can have both physical and psychological negative consequences. The aetiology of individual differences in APE is understudied, although there is reason to believe that it is partly heritable. Therefore, we aimed to estimate the heritability of APE with data from the Netherlands Twin Register (n = 8016) with classical genetic structural equation modelling. In order to use these data, we firstly investigated whether a Food Preference Questionnaire (FPQ) could measure APE with a pre-registered prestudy. Adult participants (n = 414) filled in online questionnaires, including a FPQ and measures related to APE. Spearman's rho correlation quantified the relationship between different elements of the Dutch FPQ and different scores on measures of APE. Results of the prestudy showed that the mean liking score on the FPQ could be used to measure APE (ρ > .50). This measure was then used in the main study to estimate the heritability of APE. Results showed that broad-sense heritability for APE is 49 % (additive genetic effects 14 % (95 % CI [00, 38]) + dominance genetic effects 35 % (95 % CI [11, 52]), while the remaining variance is explained by unique environmental factors. Future studies may focus on uncovering the specific genetic and unique environmental factors that play a role in APE.

Music and Genetics.

The first part of this review provides a brief historical background of behavior genetic research and how twin and genotype data can be utilized to study genetic influences on individual differences in human behavior. We then review the field of music genetics, from its emergence to large scale twin studies and the recent, first molecular genetic studies of music-related traits. In the second part of the review, we discuss the wider utility of twin and genotype data beyond estimating heritability and gene-finding. We present four examples of music studies that utilized genetically informative samples to analyze causality and gene-environmental interplay for music skills. Overall, research in the field of music genetics has gained much momentum over the last decade and its findings highlight the importance of studying both environmental and genetic factors and particularly their interplay, paving the way for exciting and fruitful times to come.

A comprehensive investigation into the genetic relationship between music engagement and mental health.

While music engagement is often regarded as beneficial for mental health, some studies report higher risk for depression and anxiety among musicians. This study investigates whether shared underlying genetic influences (genetic pleiotropy) or gene-environment interaction could be at play in the music-mental health association using measured genotypes. In 5,648 Swedish twins with information on music and sport engagement, creative achievements, self-reported mental health and psychiatric diagnoses based on nationwide patient registries, we derived polygenic scores for major depression, bipolar disorder, schizophrenia, neuroticism, sensitivity to environmental stress, depressive symptoms and general musicality. In line with phenotypic associations, individuals with higher polygenic scores for major depression and bipolar disorder were more likely to play music, practice more music and reach higher levels of general artistic achievements, while a higher genetic propensity for general musicality was marginally associated with a higher risk for a depression diagnosis. Importantly, polygenic scores for major depression and bipolar remained associated with music engagement when excluding individuals who experienced psychiatric symptoms, just as a genetic propensity for general musicality predicted a depression diagnosis regardless of whether and how much individuals played music. In addition, we found no evidence for gene-environment interaction: the phenotypic association between music engagement and mental health outcomes did not differ for individuals with different genetic vulnerability for mental health problems. Altogether, our findings suggest that mental health problems observed in musically active individuals are partly explained by a pre-existing genetic risk for depression and bipolar disorder and likely reflect horizontal pleiotropy (when one gene influences multiple traits), rather than causal influences of mental health on music engagement, or vice versa (referred to as vertical pleiotropy).

Exploring the genetics of rhythmic perception and musical engagement in the Vanderbilt Online Musicality Study.

Uncovering the genetic underpinnings of musical ability and engagement is a foundational step for exploring their wide-ranging associations with cognition, health, and neurodevelopment. Prior studies have focused on using twin and family designs, demonstrating moderate heritability of musical phenotypes. The current study used genome-wide complex trait analysis and polygenic score (PGS) approaches utilizing genotype data to examine genetic influences on two musicality traits (rhythmic perception and music engagement) in N = 1792 unrelated adults in the Vanderbilt Online Musicality Study. Meta-analyzed heritability estimates (including a replication sample of Swedish individuals) were 31% for rhythmic perception and 12% for self-reported music engagement. A PGS derived from a recent study on beat synchronization ability predicted both rhythmic perception (ß = 0.11) and music engagement (ß = 0.19) in our sample, suggesting that genetic influences underlying self-reported beat synchronization ability also influence individuals' rhythmic discrimination aptitude and the degree to which they engage in music. Cross-trait analyses revealed a modest contribution of PGSs from several nonmusical traits (from the cognitive, personality, and circadian chronotype domains) to individual differences in musicality (ß = -0.06 to 0.07). This work sheds light on the complex relationship between the genetic architecture of musical rhythm processing, beat synchronization, music engagement, and other nonmusical traits.

The Development and Validation of a Subscale for the School-Age Child Behavior CheckList to Screen for Autism Spectrum Disorder.

The first aim of this study was to construct/validate a subscale-with cut-offs considering gender/age differences-for the school-age Child Behavior CheckList (CBCL) to screen for Autism Spectrum Disorder (ASD) applying both data-driven (N = 1666) and clinician-expert (N = 15) approaches. Further, we compared these to previously established CBCL ASD profiles/subscales and DSM-oriented subscales. The second aim was to cross-validate results in two truly independent samples (N = 2445 and 886). Despite relatively low discriminative power of all subscales in the cross-validation samples, results indicated that the data-driven subscale had the best potential to screen for ASD and a similar screening potential as the DSM-oriented subscales. Given beneficial implications for pediatric/clinical practice, we encourage colleagues to continue the validation of this CBCL ASD subscale.

Music and verbal ability - a twin study of genetic and environmental associations.

Musical aptitude and music training are associated with language-related cognitive outcomes, even when controlling for general intelligence. However, genetic and environmental influences on these associations have not been studied, and it remains unclear whether music training can causally increase verbal ability. In a sample of 1,336 male twins, we tested the associations between verbal ability measured at time of conscription at age 18 and two music related variables: overall musical aptitude and total amount of music training before the age of 18. We estimated the amount of specific genetic and environmental influences on the association between verbal ability and musical aptitude, over and above the factors shared with general intelligence, using classical twin modelling. Further, we tested whether music training could causally influence verbal ability using a co-twin-control analysis. Musical aptitude and music training were significantly associated with verbal ability. Controlling for general intelligence only slightly attenuated the correlations. The partial association between musical aptitude and verbal ability, corrected for general intelligence, was mostly explained by shared genetic factors (50%) and non-shared environmental influences (35%). The co-twin-control-analysis gave no support for causal effects of early music training on verbal ability at age 18. Overall, our findings in a sizeable population sample converge with known associations between the music and language domains, while results from twin modelling suggested that this reflected a shared underlying aetiology rather than causal transfer.

Using a polygenic score in a family design to understand genetic influences on musicality.

To further our understanding of the genetics of musicality, we explored associations between a polygenic score for self-reported beat synchronization ability (PGSrhythm) and objectively measured rhythm discrimination, as well as other validated music skills and music-related traits. Using family data, we were able to further explore potential pathways of direct genetic, indirect genetic (through passive gene-environment correlation) and confounding effects (such as population structure and assortative mating). In 5648 Swedish twins, we found PGSrhythm to predict not only rhythm discrimination, but also melody and pitch discrimination (betas between 0.11 and 0.16, p < 0.001), as well as other music-related outcomes (p < 0.05). In contrast, PGSrhythm was not associated with control phenotypes not directly related to music. Associations did not deteriorate within families (N = 243), implying that indirect genetic or confounding effects did not inflate PGSrhythm effects. A correlation (r = 0.05, p < 0.001) between musical enrichment of the family childhood environment and individuals' PGSrhythm, suggests gene-environment correlation. We conclude that the PGSrhythm captures individuals' general genetic musical propensity, affecting musical behavior more likely direct than through indirect or confounding effects.

Sex, Drugs, and Genes: Illuminating the Moral Condemnation of Recreational Drugs.

Over the past decade, evolutionary psychologists have proposed that many moral stances function to promote self-interests. At the same time, behavioral geneticists have demonstrated that many moral stances have genetic bases. We integrated these perspectives by examining how moral condemnation of recreational drug use relates to sexual strategy (i.e., being more vs. less open to sex outside of a committed relationship) in a sample of Finnish twins and siblings (N = 8,118). Twin modeling suggested that genetic factors accounted for 53%, 46%, and 41% of the variance in drug condemnation, sociosexuality, and sexual-disgust sensitivity, respectively. Further, approximately 75% of the phenotypic covariance between drug condemnation and sexual strategy was accounted for by genes, and there was substantial overlap in the genetic effects underlying both drug condemnation and sexual strategy (rg = .41). Results are consistent with the proposal that some moral sentiments are calibrated to promote strategic sexual interests, which arise partially via genetic factors.

How genetic and environmental variance in personality traits shift across the life span: Evidence from a cross-national twin study.

Decades of research have shown that about half of individual differences in personality traits is heritable. Recent studies have reported that heritability is not fixed, but instead decreases across the life span. However, findings are inconsistent and it is yet unclear whether these trends are because of a waning importance of heritable tendencies, attributable to cumulative experiential influences with age, or because of nonlinear patterns suggesting Gene × Environment interplay. We combined four twin samples (N = 7,026) from Croatia, Finland, Germany, and the United Kingdom, and we examined age trends in genetic and environmental variance in the six HEXACO personality traits: Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness, and Openness. The cross-national sample ranges in age from 14 to 90 years, allowing analyses of linear and nonlinear age differences in genetic and environmental components of trait variance, after controlling for gender and national differences. The amount of genetic variance in Extraversion, Agreeableness, and Openness followed a reversed U-shaped pattern across age, showed a declining trend for Honesty-Humility and Conscientiousness, and was stable for Emotionality. For most traits, findings provided evidence for an increasing relative importance of life experiences contributing to personality differences across the life span. The findings are discussed against the background of Gene × Environment transactions and interactions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Why Is an Early Start of Training Related to Musical Skills in Adulthood? A Genetically Informative Study.

Experts in domains such as music or sports often start training early. It has been suggested that this may reflect a sensitive period in childhood for skill acquisition. However, it could be that familial factors (e.g., genetics) contribute to the association. Here, we examined the effect of age of onset of musical training on musical aptitude and achievement in professional musicians (n = 310) and twins (n = 7,786). In line with previous literature, results showed that an earlier age of onset was associated with higher aptitude and achievement in both samples. After we adjusted for lifetime practice hours, age of onset was associated only with aptitude (p < .001; achievement: p > .14). Twin analyses showed that the association with aptitude was fully explained by familial factors. Thus, these findings provide little support for a sensitive period for music but highlight that familiar factors play an important role for associations between age of onset of training and skills in adulthood.

The effects of playing music on mental health outcomes.

The association between active musical engagement (as leisure activity or professionally) and mental health is still unclear, with earlier studies reporting contrasting findings. Here we tested whether musical engagement predicts (1) a diagnosis of depression, anxiety, schizophrenia, bipolar or stress-related disorders based on nationwide patient registers or (2) self-reported depressive, burnout and schizotypal symptoms in 10,776 Swedish twins. Information was available on the years individuals played an instrument, including their start and stop date if applicable, and their level of achievement. Survival analyses were used to test the effect of musical engagement on the incidence of psychiatric disorders. Regression analyses were applied for self-reported psychiatric symptoms. Additionally, we conducted co-twin control analyses to further explore the association while controlling for genetic and shared environmental confounding. Results showed that overall individuals playing a musical instrument (independent of their musical achievement) may have a somewhat increased risk for mental health problems, though only significant for self-reported mental health measures. When controlling for familial liability associations diminished, suggesting that the association is likely not due to a causal negative effect of playing music, but rather to shared underlying environmental or genetic factors influencing both musicianship and mental health problems.

Gene-environment interaction in expertise: The importance of childhood environment for musical achievement.

Both genes and the environment are important for individual differences in expertise, but little is known about gene-environment interactions underlying domain-specific achievement. Here we explored this issue in a large Swedish twin cohort (N = 6,610), using moderator modeling with musical expertise as a model domain. Specifically, we tested whether musical enrichment of the childhood environment moderates adult musical achievement, as well as the magnitude of genetic and nongenetic influences on individual differences in achievement. Musical achievement was measured using the Creative Achievement Questionnaire and enrichment of the childhood environment was indexed with a principal component derived from the number of music records in the family home, number of individuals in the family environment playing an instrument, frequency of concert visits, and music education before the age of 12. As expected, we found a positive association between childhood musical enrichment and musical achievement in adulthood. Interestingly, however, the total variance in musical achievement as well as the relative importance of genetic influences increased with a higher level of musical enrichment. Estimates of genetic and environmental influences as well as the magnitude of the environmental moderation differed for men and women. These findings suggest that, in line with recent multifactorial models of expert performance, a musically enriched childhood environment amplifies individual differences, an effect which is largely driven by an increase in the importance of genetic factors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Do Parental Psychiatric Symptoms Predict Outcome in Children With Psychiatric Disorders? A Naturalistic Clinical Study.

OBJECTIVE: Parental psychiatric symptoms can negatively affect the outcome of children's psychopathology. Studies thus far have mainly shown a negative effect of maternal depression. This study examined the associations between a broad range of psychiatric symptoms in mothers and fathers and the child's outcome. METHOD: Internalizing and externalizing psychiatric symptoms were assessed in 742 mothers, 440 fathers, and their 811 children at the first evaluation in 3 child and adolescent psychiatric outpatient clinics and at follow-up (on average 1.7 years later). Predictions of child's symptoms scores were tested at follow-up by parental symptom scores at baseline, parental scores at follow-up, and offspring scores at baseline. RESULTS: Children whose mother or father scored above the (sub)clinical threshold for psychiatric symptoms at baseline had higher symptom scores at baseline and at follow-up. Offspring follow-up scores were most strongly predicted by offspring baseline scores, in addition to parental psychiatric symptoms at follow-up. Offspring symptom scores at follow-up generally were not predicted by parental scores at baseline. Maternal and paternal associations were of similar magnitude. CONCLUSION: Higher symptom scores at follow-up in children of parents with psychopathology were mainly explained by higher symptom scores at baseline. Continuing parent-offspring associations could be a result of reciprocal effects, ie, parental symptoms influencing offspring symptoms and offspring symptoms influencing parental symptoms. Nevertheless, the results show that these children are at risk for persisting symptoms, possibly indicating the need to treat maternal and paternal psychopathology.

Genetic and environmental influences on conduct and antisocial personality problems in childhood, adolescence, and adulthood.

Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and unique environmental factors on variation in conduct problems measured at childhood and adolescence and antisocial personality problems measured at adulthood and on the covariation across ages. We also tested whether these estimates differed by sex. Longitudinal data were collected in the Netherlands Twin Register over a period of 27 years. Age appropriate and comparable measures of conduct and antisocial personality problems, assessed with the Achenbach System of Empirically Based Assessment, were available for 9783 9-10-year-old, 6839 13-18-year-old, and 7909 19-65-year-old twin pairs, respectively; 5114 twins have two or more assessments. At all ages, men scored higher than women. There were no sex differences in the estimates of the genetic and environmental influences. During childhood, genetic and environmental factors shared by children in families explained 43 and 44% of the variance of conduct problems, with the remaining variance due to unique environment. During adolescence and adulthood, genetic and unique environmental factors equally explained the variation. Longitudinal correlations across age varied between 0.20 and 0.38 and were mainly due to stable genetic factors. We conclude that shared environment is mainly of importance during childhood, while genetic factors contribute to variation in conduct and antisocial personality problems at all ages, and also underlie its stability over age.

Heritability of Behavioral Problems in 7-Year Olds Based on Shared and Unique Aspects of Parental Views.

In studies of child psychopathology, phenotypes of interest are often obtained by parental ratings. When behavioral ratings are obtained in the context of a twin study, this allows for the decomposition of the phenotypic variance, into a genetic and a non-genetic part. If a phenotype is assessed by a single rater, heritability is based on the child's behavior as expressed in the presence of that particular rater, whereas heritability based on assessments by multiple raters allows for the estimation of the heritability of the phenotype based on rater agreement, as well as the heritability of the rater specific view of the behavior. The aim of this twin study was to quantify the rater common and rater specific contributions to the variation in children's behavioral problems. We estimated the heritability of maternal and paternal ratings of the Child Behavior Checklist (CBCL) 6-18 empirical emotional and behavioral problem scales in a large sample of 12,310 7-year old Dutch twin pairs. Between 30 and 59% of variation in the part of the phenotype parents agree upon was explained by genetic effects. Common environmental effects that make children in the same family similar explained less variance, ranging between 0 and 32%. For unique views of their children's behavioral problems, heritability ranged between 0 and 20% for maternal and between 0 and 22% for paternal views. Between 7 and 24% of the variance was accounted for by common environmental factors specific to mother and father's views. The proportion of rater shared and rater specific heritability can be translated into genetic correlations between parental views and inform the design and interpretation of results of molecular genetic studies. Genetic correlations were nearly or above 0.7 for all CBCL based psychopathology scales. Such large genetic correlations suggest two practical guidelines for genome-wide association studies (GWAS): when studies have collected data from either fathers or mothers, the shared genetic aetiology in parental ratings indicates that is possible to analyze paternal and maternal assessments in a single GWAS or meta-analysis. Secondly, if a study has collected information from both parents, a gain in statistical power may be realized in GWAS by the simultaneous analysis of the data.