Blessed are the meek for they shall inherit the earth: quietness component of introversion is associated with single nucleotide polymorphisms in two circadian clock genes

Individual differences studied by chronobiologists and personality psychologists are usually shaped by polygenic selection occurring by small allele frequency shifts spreading across many loci. Therefore, the candidate gene association studies suffer from increased likelihood of false positive findings. We previously associated a PER3 single nucleotide polymorphism (SNP, rs228697) with self-ratings on personality-relevant nouns exemplifying personality dimension of Extraversion/Introversion in a sample of 88 female students. To replicate and extend this finding, we genotyped three more SNPs in three circadian clock genes. The results indicated that the minor alleles of PER3 rs228697 and PER2 rs934945 were rather similar in terms of their association with a personality type nicknamed “demure persona” (i.e. described by such nouns as “quietness”, “restraint”, “taciturnity”, “bashfulness”, “timidity”, “constraint”, and “reticence”). Analysis of data from populations of the 1000 Genomes Project suggested that, like frequencies of the minor alleles of many SNPs in circadian clock genes, the frequencies of these two SNPs were higher in populations of out-of-African ancestry compared to populations of African ancestry. We suggested that genetic candidates for Extraversion/Introversion can be prioritized in future association studies by means of identification of genetic signatures of polygenic selection imposed by out-of-Africa expansion of ancestral populations.     

Higher scores in the extraversion personality trait are associated with a functional polymorphism in the PER3 gene in healthy subjects

A polymorphism in the PER3 (period circadian clock 3) gene has been associated with neuropsychiatric disorders and endophenotypes. We evaluated the possible association of personality domains with the PER3 polymorphism in a sample of healthy subjects: 271 individuals were evaluated with the Big Five Inventory and genotyped for the PER3 Variable Number Tandem Repeat (VNTR) polymorphism. We found a significant association between the PER3 polymorphism and the extraversion personality trait (p = 0.0093). The 5/5 genotype carriers showed higher scores for extraversion. This is the first time that a significant association between the PER3 VNTR polymorphism and extraversion is reported.     

Lifetime low behavioural plasticity of personality traits in the common vole (Microtus arvalis) under laboratory conditions

Individual differences in behaviour, referred to as animal personality, are consistent across time and contexts. Nevertheless, personality traits show behavioural plasticity, much like many other phenotypic traits. In the present study, we examined the relationship between personality traits and behavioural plasticity in the common vole (Microtus arvalis) under stable, long-lasting laboratory conditions. A total of 94 voles were tested in the classic open field test, designed to measure seven behavioural parameters (distance moved, grooming, immobility, rearing, running, scanning and walking duration) during a three-minute test. A total of 60 voles formed the experimental group and were tested at four different time points over their lifetime (1st, 3rd, 5th and 7th month); 34 voles formed the control group and were tested only once at the 7th month. All voles were of the same age. Based on principal component analysis (PCA), two ordination axes were determined: “exploration” and “activity.” For further analyses, “distance moved” and “scanning duration” were selected from the first axis and “walking duration” from the second. Using linear mixed-effect models (LMMs), we found highly significant random intercepts (i.e. personality traits) in all three behavioural parameters. However, evidence for behavioural plasticity was only found in the distance moved parameter, as determined from the random slope, and correlations between personality trait (intercept) and plasticity (slope) were not significant for any trait. During the experiment, variances of random effects were high and remained essentially the same, whilst the rank order of many individuals changed. Based on fixed effect slopes and a comparison with the control group, habituation was only significant for “walking duration.” The observed low behavioural plasticity could mirror stable (laboratory) conditions that result in the manifestation of original trait settings (genetic, early postnatal) or their gradual overcoming. These findings provide a starting point for further tests on free-living voles.     

Genetic variation in the hypothalamic-pituitary-adrenocortical axis regulatory factor, T-box 19, and the angry/hostility personality trait

Neurotic personality traits are important factors in several psychiatric disorders and suicidal behavior. Here, we have investigated the existence of potential relationships between neurotic personality traits and genetic variation. Non-suicidal parents derived from trios (suicide attempter and both parents) and non-suicidal volunteers, examined by the Neuroticism, Extraversion and Openness (NEO) Personality Inventory - Revised (NEO PI-R), were divided into screening and replication samples. The screening sample (n= 127) was used to select potential relationships between neurotic personality traits and genetic variation among 130 single nucleotide polymorphisms (SNPs). Screening (analysis of variance) with regard to the personality dimension neuroticism indicated potential relationships at three different loci. More detailed analysis of these three SNPs at NEO PI-R facet level indicated four potential relationships. T-test analysis in the replication sample (n= 617) was used to retest the relationships indicated during screening. One of those relationships was confirmed in the replication sample (P= 0.0052; Bonferroni correction), indicating that genetic variation at the human T-box 19 (TBX19) locus is related to the personality trait angry/hostility. Furthermore, using analysis of haplotypes among trios by transmission disequilibrium test and its extension, the family-based association test, overtransmission of a haplotype GAC at the TBX19 locus was associated with increased angry/hostility scores among suicide attempters (P= 0.009; Bonferroni correction). This is to our knowledge the first report on the association of the angry hostility personality trait with genetic variation at the TBX19 locus, an important regulator of the hypothalamic-pituitary-adrenocortical axis.     

Wild GWAS—association mapping in natural populations

The increasing affordability of sequencing and genotyping technologies has transformed the field of molecular ecology in recent decades. By correlating marker variants with trait variation using association analysis, large‐scale genotyping and phenotyping of individuals from wild populations has enabled the identification of genomic regions that contribute to phenotypic differences among individuals. Such “gene mapping” studies are enabling us to better predict evolutionary potential and the ability of populations to adapt to challenges, such as changing environment. These studies are also allowing us to gain insight into the evolutionary processes maintaining variation in natural populations, to better understand genotype‐by‐environment and epistatic interactions and to track the dynamics of allele frequency change at loci contributing to traits under selection. Gene mapping in the wild using genomewide association scans (GWAS) do, however, come with a number of methodological challenges, not least the population structure in space and time inherent to natural populations. We here provide an overview of these challenges, summarize the exciting methodological advances and applications of association mapping in natural populations reported in this special issue and provide some guidelines for future “wild GWAS” research.     

AVPR1A Variation in Chimpanzees (Pan troglodytes): Population Differences and Association with Behavioral Style

Primates and other mammals show measurable, heritable variation in behavioral traits such as gregariousness, timidity, and aggression. Connections among behavior, environment, neuroanatomy, and genetics are complex, but small genetic differences can have large effects on behavioral phenotypes. One of the best examples of a single gene with large effects on natural variation in social behavior is AVPR1A, which codes for a receptor of the peptide hormone arginine vasopressin. Work on rodents shows a likely causal association between AVPR1A regulatory polymorphisms and social behavior. Chimpanzees also show variation in the AVPR1A regulatory region, with some individuals lacking a ca. 350-bp segment corresponding to a putative functional element. Thus, chimpanzees have a “short” allele (segment deletion) and a “long” allele (no deletion) at this locus. Here we compare AVPR1A variation in two chimpanzee populations, and we examine behavioral and hormonal data in relation to AVPR1A genotypes. We genotyped AVPR1A in a captive population of western chimpanzees (Pan troglodytes verus, New Iberia Research Center; N = 64) for which we had quantitative measures of personality (based on 15 behavioral style indices, calculated from 3 yr of observational data), dominance rank, and baseline testosterone levels. We also provide the first assessment of AVPR1A genotype frequencies in a wild eastern chimpanzee population (Pan troglodytes schweinfurthii, Ngogo community, Kibale National Park, Uganda; N = 26). Our results indicated that the AVPR1A long allele was associated with a “smart” social personality in captive western chimpanzees, independent of testosterone levels. Although the frequency of the long allele was relatively low in captive western chimpanzees (0.23), it was the major allele in wild eastern chimpanzees (0.62). Our finding that allele and genotype frequencies for the AVPR1A polymorphism differ among chimpanzee populations also highlights the need for comparative studies —across subspecies and research sites— in primate behavioral genetics.     

Two shades of boldness: novel object and anti-predator behavior reflect different personality dimensions in domestic rabbits

It is increasingly common to quantify and describe behavioral variation in domestic and wild animals in terms of “personality”. Correlating behavioral traits are referred to as personality “dimensions” or “factors” and different dimensions have been reported in different species. “Boldness” is a well-described personality dimension in several species, although some issues remain unclear. Previous models of boldness include both novelty and risk taking, but recent studies indicate that these types of behaviors may reflect separate personality dimensions. In this study, we developed a behavioral test battery for domestic rabbits, and recorded behaviors of 61 individuals in four different situations (novel object, novel arena, social, and predator interactions). We used domestic rabbits as a model because behavioral variation in rabbits has rarely been quantified in terms of personality dimensions, although rabbit behavior is described. We also wanted to investigate behavioral variation in a Swedish rabbit breed of conservation concern — the Gotland rabbit. Factor analysis of the behavioral test measures suggested three personality dimensions: “exploration”, “boldness”, and “anxiety”. Novel object scores clustered in the exploration and boldness factors, whereas scores associated with predator interactions were explained by “anxiety”, indicating that novel object and anti-predator behavior reflect different personality dimensions in rabbits.     

HOW SPECIFICITY AND EPIDEMIOLOGY DRIVE THE COEVOLUTION OF STATIC TRAIT DIVERSITY IN HOSTS AND PARASITES

There is typically considerable variation in the level of infectivity of parasites and the degree of resistance of hosts within populations. This trait variation is critical not only to the evolutionary dynamics but also to the epidemiology, and potentially the control of infectious disease. However, we lack an understanding of the processes that generate and maintain this trait diversity. We examine theoretically how epidemiological feedbacks and the characteristics of the interaction between host types and parasites strains determine the coevolution of host–parasite diversity. The interactions include continuous characterizations of the key phenotypic features of classic gene‐for‐gene and matching allele models. We show that when there are costs to resistance in the hosts and infectivity in the parasite, epidemiological feedbacks may generate diversity but this is limited to dimorphism, often of extreme types, in a broad range of realistic infection scenarios. For trait polymorphism, there needs to be both specificity of infection between host types and parasite strains as well as incompatibility between particular strains and types. We emphasize that although the high specificity is well known to promote temporal “Red Queen” diversity, it is costs and combinations of hosts and parasites that cannot infect that will promote static trait diversity.     

MAINTENANCE OF GENETIC VARIATION IN HUMAN PERSONALITY: TESTING EVOLUTIONARY MODELS BY ESTIMATING HERITABILITY DUE TO COMMON CAUSAL VARIANTS AND INVESTIGATING THE EFFECT OF DISTANT INBREEDING

Personality traits are basic dimensions of behavioral variation, and twin, family, and adoption studies show that around 30% of the between‐individual variation is due to genetic variation. There is rapidly growing interest in understanding the evolutionary basis of this genetic variation. Several evolutionary mechanisms could explain how genetic variation is maintained in traits, and each of these makes predictions in terms of the relative contribution of rare and common genetic variants to personality variation, the magnitude of nonadditive genetic influences, and whether personality is affected by inbreeding. Using genome‐wide single nucleotide polymorphism (SNP) data from > 8000 individuals, we estimated that little variation in the Cloninger personality dimensions (7.2% on average) is due to the combined effect of common, additive genetic variants across the genome, suggesting that most heritable variation in personality is due to rare variant effects and/or a combination of dominance and epistasis. Furthermore, higher levels of inbreeding were associated with less socially desirable personality trait levels in three of the four personality dimensions. These findings are consistent with genetic variation in personality traits having been maintained by mutation–selection balance.     

Sexual selection and animal personality

Consistent individual behavioural tendencies, termed “personalities”, have been identified in a wide range of animals. Functional explanations for personality have been proposed, but as yet, very little consideration has been given to a possible role for sexual selection in maintaining differences in personality and its stability within individuals. We provide an overview of the available literature on the role of personality traits in intrasexual competition and mate choice in both human and non‐human animals and integrate this into a framework for considering how sexual selection can generate and maintain personality. For this, we consider the evolution and maintenance of both main aspects of animal personality: inter‐individual variation and intra‐individual consistency.     

Personality is reflected in the brain's intrinsic functional architecture

Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC) can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective 'hubs' in the brain--the anterior cingulate and precuneus--each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses.     

Does inbreeding affect personality traits?

The question of why variation is maintained in personality traits is an evolutionary puzzle. According to the condition‐dependence hypothesis, such traits depend on condition, which limits the behavioral choices available to individuals. Because condition is affected by many genes, it can effectively be manipulated by inbreeding, which exposes the effects of deleterious recessive mutations. Here, I compared two personality traits, boldness and tendency to explore, of male guppies (Poecilia reticulata) from first‐generation inbred and outbred treatments. Boldness in guppies is associated with increased sexual attractiveness and is thus expected to affect fitness. Therefore, I hypothesized that the personality traits would be negatively affected by inbreeding. However, the results indicated that inbred guppies did not differ in either personality trait from their outbred counterparts. This finding suggests that mechanisms other than condition dependence are maintaining personality variation in the guppy.     

Evolution of a length polymorphism in the human PER3 gene, a component of the circadian system

Period homologue 3 (PER3) is a component of the mammalian circa-dian system, although its precise role is unknown. A biallelic variable number tandem repeat (VNTR) polymorphism exists in human PER3, consisting of 4 or 5 repeats of a 54-bp sequence in a region encoding a putative phosphorylation domain. This polymorphism has previously been reported to associate with diurnal preference ("morningness" and "eveningness") and delayed sleep-phase syndrome. We have investigated the global allele frequencies of this variant in ethnically distinct indigenous populations. All populations were polymorphic, with the shorter (4-repeat) allele ranging in frequency from 0.19 (Papua New Guinea) to 0.89 (Mongolia). To investigate if allele frequency has been influenced by natural selection, the authors 1) tested for a correlation with latitude and mean annual insolation (incident sunlight energy), using classical markers to correct for historical population differentiation; and they 2) compared allele-frequency difference between European American, African American, and East Asian populations, as measured using F(ST), to an empirical null distribution of F(ST)values based on a genome-wide dataset of single nucleotide polymorphisms (SNPs) of presumed neutral loci that were previously typed by The SNP Consortium. The variation in allele frequencies between indigenous populations did not show a pattern that would indicate selective pressure on PER3resulting from day-length variation or mean annual insolation, and the allele-frequency difference between European Americans, African Americans, and East Asians was not an outlier when compared to the distribution for presumed neutral SNPs. We therefore find no evidence for differential or balancing selection in the contemporary pattern of global PER3allele frequencies.     

Personality endophenotypes for bipolar affective disorder: a family-based genetic association analysis

Genetic analyses of complex conditions such as bipolar disorder (BD) may be facilitated by the use of intermediate phenotypes. Various personality traits are overrepresented in people with BD and their unaffected relatives, and may constitute genetically transmitted risk factors or endophenotypes of the illness. In this study, we administered a battery of seven different personality questionnaires comprising 19 subscales to 31 Caucasian BD families (n = 241). Ten of these personality traits showed significant evidence of heritability and were therefore selected as candidate endophenotypes. In addition, a principal components analysis produced two heritable components (negative affect and appetitive drive), which accounted for a considerable proportion of the variance (29% + 12%) and were also used in the analysis. A family-based quantitative association study was carried out using the orthogonal model from the quantitative transmission disequilibrium tests (QTDT) program. Monte Carlo permutations (M = 500), which allow for non-normal data and provide a global P value, corrected for multiple testing, were used to calculate empirical P values for the within-family component of association. The 3' untranslated region repeat polymorphism of the dopamine transporter gene (SLC6A3) was associated with self-directedness (P < 0.0001) and negative affect (P = 0.010). The short allele of the serotonin transporter gene (SLC6A4) promoter polymorphism showed a trend toward association with higher harm avoidance (P = 0.016) and negative affect (P = 0.028). The catechol-o-methyltransferase val158met polymorphism was weakly associated with the personality traits, 'Spirituality' (P = 0.040) and irritable temperament (P = 0.022). Furthermore, the met allele of the brain-derived neurotrophic factor val66met polymorphism was associated with higher hyperthymic temperament scores. We raise the possibility that the 10R allele of the SLC6A3 repeat polymorphism and the short allele of the SLC6A4 promoter variant constitute risk factors for irritable-aggressive and anxious-dysthymic subtypes of BD, respectively.     

The genetic contribution to canine personality

The domestic dog may be exceptionally well suited for behavioral genetic studies owing to its population history and the striking behavior differences among breeds. To explore to what extent and how behavioral traits are transmitted between generations, heritabilities and genetic correlations for behavioral traits were estimated in a cohort containing over 10,000 behaviorally tested German shepherd and Rottweiler dogs. In both breeds, the pattern of co-inheritance was found to be similar for the 16 examined behavioral traits. Furthermore, over 50% of the additive genetic variation of the behavioral traits could be explained by one underlying principal component, indicating a shared genetic component behind most of the examined behavioral traits. Only aggression appears to be inherited independently of the other traits. The results support a genetic basis for a broad personality trait previously named shyness-boldness dimension, and heritability was estimated to be 0.25 in the two breeds. Therefore, breeds of dogs appear to constitute a valuable resource for behavioral genetic research on the normal behavioral differences in broad personality traits.     

Circadian gene variants influence sleep and the sleep electroencephalogram in humans

The sleep electroencephalogram (EEG) is highly heritable in humans and yet little is known about the genetic basis of inter-individual differences in sleep architecture. The aim of this study was to identify associations between candidate circadian gene variants and the polysomnogram, recorded under highly controlled laboratory conditions during a baseline, overnight, 8 h sleep opportunity. A candidate gene approach was employed to analyze single-nucleotide polymorphisms from five circadian-related genes in a two-phase analysis of 84 healthy young adults (28 F; 23.21 ± 2.97 years) of European ancestry. A common variant in Period2 (PER2) was associated with 20 min less slow-wave sleep (SWS) in carriers of the minor allele than in noncarriers, representing a 22% reduction in SWS duration. Moreover, spectral analysis in a subset of participants (n = 37) showed the same PER2 polymorphism was associated with reduced EEG power density in the low delta range (0.25–1.0 Hz) during non-REM sleep and lower slow-wave activity (0.75–4.5 Hz) in the early part of the sleep episode. These results indicate the involvement of PER2 in the homeostatic process of sleep. Additionally, a rare variant in Melatonin Receptor 1B was associated with longer REM sleep latency, with minor allele carriers exhibiting an average of 65 min (87%) longer latency from sleep onset to REM sleep, compared to noncarriers. These findings suggest that circadian-related genes can modulate sleep architecture and the sleep EEG, including specific parameters previously implicated in the homeostatic regulation of sleep.     

EVOLUTION OF STATIC ALLOMETRIES: ADAPTIVE CHANGE IN ALLOMETRIC SLOPES OF EYE SPAN IN STALK‐EYED FLIES

Julian Huxley showed that within‐species (static) allometric (power‐law) relations can arise from proportional growth regulation with the exponent in the power law equaling the factor of proportionality. Allometric exponents may therefore be hard to change and act as constraints on the independent evolution of traits. In apparent contradiction to this, many empirical studies have concluded that static allometries are evolvable. Many of these studies have been based, however, on a broad definition of allometry that includes any monotonic shape change with size, and do not falsify the hypothesis of constrained narrow‐sense allometry. Here, we present the first phylogenetic comparative study of narrow‐sense allometric exponents based on a reanalysis of data on eye span and body size in stalk‐eyed flies (Diopsidae). Consistent with a role in sexual selection, we found strong evidence that male slopes were tracking “optima” based on sexual dimorphism and relative male trait size. This tracking was slow, however, with estimated times of 2–3 million years for adaptation to exceed ancestral influence on the trait. Our results are therefore consistent with adaptive evolution on million‐year time scales, but cannot rule out that static allometry may act as a constraint on eye‐span adaptation at shorter time scales.     

An integrative study of facultative personality calibration

The theory of facultative calibration, which explains personality differences as responses to variation in other phenotypic traits of individuals, received mixed results throughout the last years. Whereas there is strong evidence that individual differences in human behavior are correlated with the self-perception of other traits, it still needs to be questioned whether they are also adjusted to objective differences in body condition (i.e. formidability). In two independent studies (N₁?=?119 men and 124 women, N₂?=?165 men) we tested hypotheses of facultative personality calibration in an integrative way, assessing various outcomes of previous studies in the same samples (including Anger Proneness, Extraversion, Neuroticism, Narcissism, Shyness, Vengefulness, and Sociosexual Orientation). Formidability was derived from assessments of physical strength and various anthropometric measures from full-body 3D scans and paired with measures of self-perceived and other-rated physical attractiveness (based on rotating morphometric 3D body models and facial photographs). We could replicate positive correlations with self-perceived attractiveness across outcomes, though these were not corroborated by more objective assessments of attractiveness: an effect of other-rated attractiveness was clearly not supported in our results for either sex, regardless of the personality outcome. Anthropometric measures and physical strength were also largely unrelated to personality, with the exception of Extraversion, Utility of Personal Aggression, and Sociosexual Orientation. While the two samples differed in their results for domain-level Extraversion, at least the Extraversion facets Activity and Assertiveness were related to strength and masculinity in men. For Sociosexual Orientation the results of our two samples varied more substantially, a positive association was only present in Study 2. Future studies need to clarify whether formidability, potentially an indicator of genetic quality for males, enhances their orientation and success in short-term mating. Furthermore we propose longitudinal twin-difference studies as means to evaluate the theory of personality recalibration in a more controlled manner.