Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.

Mutations in Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) and Cyclin-Dependent Kinase 4 (CDK4) contribute to susceptibility in approximately 40% of high-density cutaneous melanoma (CMM) families and about 2% of unselected CMM cases. BRCA-1 associated protein-1 (BAP1) has been more recently shown to predispose to CMM and uveal melanoma (UMM) in some families; however, its contribution to CMM development in the general population is unreported. We sought to determine the contribution of these genes to CMM susceptibility in a population-based sample of cases from Australia. We genotyped 1,109 probands from Queensland families and found that approximately 1.31% harbored mutations in CDKN2A, including some with novel missense mutations (p.R22W, p.G35R and p.I49F). BAP1 missense variants occurred in 0.63% of cases but no CDK4 variants were observed in the sample. This is the first estimate of the contribution of BAP1 and CDK4 to a population-based sample of CMM and supports the previously reported estimate of CDKN2A germline mutation prevalence.

The phenotypic (observed), genetic, and environmental correlations were examined in a sample of adult twins between the four factors and global score of the trait emotional intelligence questionnaire (TEIQue) and the seven vocational interest factors of the Jackson Career Explorer (JCE). Multiple significant correlations were found involving the work style vocational interest factor (consisting of job security, stamina, accountability, planfulness, and interpersonal confidence) and the social vocational interest factor (which included interests in the social sciences, personal services, teaching, social services, and elementary education), both of which correlated significantly with all of the TEIQue variables (well-being, self-control, emotionality, sociability, and global trait EI). Following bivariate genetic analyses, most of the significant phenotypic correlations were found to also have significant genetic correlations as well as significant non-shared (unique) environmental correlations.

This article reports the first behavioral genetic study of relationships between alexithymia and four styles of humor: affiliative, self-enhancing, self-defeating, and aggressive. A total of 509 MZ pairs and 264 DZ pairs of twins completed the Toronto Alexithymia Scale-20 (TAS-20) and the Humor Styles Questionnaire (HSQ). Consistent with our predictions, alexithymia correlated negatively with affiliative and self-enhancing humor and positively with self-defeating and aggressive humor. All but one of the 16 phenotypic correlations that we report are significant at the 0.01 level. Also consistent with our predictions, the phenotypic correlations between alexithymia and humor styles were primarily attributable to correlated genetic factors and to a lesser extent to correlated non-shared environmental factors. Correlated shared environmental factors had no significant effect. Implications and limitations of this study are discussed.

In singletons, asthma may be associated with shorter height and delayed growth during adolescence. Yet, these studies do not account for heritability of asthma, puberty/menarche, and height. We aimed to study the association between asthma and puberty in boys and menarche in girls, and height, in a cohort of twins and subsequently in same-sex twin pairs discordant for asthma. From a Swedish twin cohort, parent- and self-reported data on asthma, puberty/menarche, and height were collected. Pubertal staging was established via the Petersen index. Logistic and linear regression was used to estimate associations between asthma and puberty/menarche and height, respectively. For within-pair analyses in twins discordant for asthma, conditional logistic and linear regression were used. Data on 2,658 (49.1% boys) twins were included. Among boys, asthma prevalence was 8.2% at 8–9 years and 10.2% at 13–14 years. Corresponding numbers for girls were 4.2% and 4.9%, respectively. In the entire cohort, no statistically significant associations were found between current asthma and puberty/menarche. Boys with asthma were shorter than boys without asthma at 8–9 years (on average, 1.86 [0.17–3.56] cm, p = .03) and at 13–14 years (on average, 2.94 [0.98–4.91] cm, p = .003) but not at 19–20 years. No such associations were found for girls. Within same-sex twin pairs discordant for asthma, no statistically significant associations were found for either sex. Twin boys, but not girls, with asthma were shorter than those without asthma. Non-statistically significant estimates from within-pair analyses suggest the association is partly confounded by genetic or familial environmental factors.

We aimed to assess the non-genetic contribution to the associations between the change in weight and changes in cardiovascular disease (CVD) risk factors. This analysis included 194 Korean monozygotic (MZ) twin pairs (116 men, 272 women; mean age, 38.5 ± 6.8 years) who were first examined for weight and CVD risk factors (blood pressure (BP), glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)) between December 2005 and December 2008, and returned for a repeat examination after 2.7 ± 0.9 years. The within-pair correlations were 0.21 for the change in weight and 0.05-0.42 for the changes in CVD risk factors. Bivariate analyses showed significant environmental correlations shared between the change in weight and the changes in CVD risk factors (p < .05), except for glucose, while there were no significant genetic effects shared between the phenotypes. After adjusting for baseline values of weight, smoking, and alcohol consumption, diastolic blood pressure (DBP), TG, TC, and LDL significantly increased by 1.6 mmHg, 0.09 mmol/L, 0.10 mmol/L, and 0.09 mmol/L, respectively, per 1 kg increase in within-pair differences in weight change. In Korean MZ twins, similarity between twins for changes in weight and CVD risk factors were small to moderate, and non-genetic factors were responsible for the associations between the change in weight and changes in DBP, TG, TC, and LDL.

The genetic contribution of blood pressure and heart rate (HR) varied widely between studies. Demographic factors such as ethnicity, age and/or sex might explain some of the heterogeneity. We performed a systematic review focusing on four phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), HR and pulse pressure (PP). Meta-regression was conducted to analyze potential factors in relation to SBP and DBP heritability. A total of 10,613 independent twins that came from 17 studies were included in the analysis. The weighted mean value of heritability for SBP and DBP was 0.54 (95% CIs: 0.48–0.60) and 0.49 (95% CIs: 0.42–0.56). Comparatively, three studies of HR and four studies of PP heritability were limited for the heterogeneity test. Meta-regression showed that, on average, SBP heritability with additive genes/unique environment (AE) model tend to have a higher heritability than additive genes/shared environment/unique environment (ACE) model (coefficient = 0.0947, p = .0142). A similar result was found for DBP as well. No other factors such as sex, age, ethnicity, publication year were significantly associated with heritability variance. Our study shows heritability estimates based on twin studies of both SBP and DBP are around 50%, using an AE rather than an ACE model; the variance due to C ended up in A, suggesting that the AE model may overestimate heritability if a small contribution of shared environment exists.

Objective: Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. Method: We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Results: Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. Conclusions: There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.

The aim of the present article was to study the prevalence and the heritability of the initiation of breastfeeding in the Netherlands. The study was carried out in 5,581 participants from the Netherlands Twin Register, and included female twins, their sisters and mothers. All of the participants were born between 1911 and 1991. Breastfeeding was self-reported by the participants, and its prevalence was estimated conditional on birth cohort (born before 1955, 1955–1964, 1965–1974, 1975, or later). To estimate the heritability, we conducted extended twin-family modeling using the SEM package OpenMx in R. Mothers of twins had lower prevalence to initiate breastfeeding and the prevalence of initiation of breastfeeding increased with birth cohort: among mothers of twins 66% in the oldest (pre-1955) to 74% in the youngest (post-1974) and among mothers, who were twins themselves or sisters of twins, 79% in the oldest (pre-1955) to 85% in the youngest (post-1974). When accounting for prevalence differences between mothers of twins and other women, heritability of initiation of breastfeeding was 70%. However, the familial resemblance for sister and mother-daughter pairs was clearly lower than for DZ twin pairs, but as the number of non-twin sisters was relatively low, this observation did not lead to a significant contribution of a special shared twin environment.

Chronic widespread pain (CWP) is a common disorder affecting up to 15% of the general population. The objective of the present study was to explore the role of previously reported psychosocial and interpersonal risk factors on variation in CWP by investigating CWP discordant monozygotic (MZ) twins. This approach allows separation of cause and effect relationships, albeit imperfectly, as well the control for critical confounding variables such as common environment or genetics. In a total sample of N = 3,266 female twins aged 18–89 years, MZ (113 full pairs) and DZ twins (180 full pairs) discordant for CWP were selected. Items from the London fibromyalgia symptom screening questionnaire were used to discriminate cases from controls. To assess potential risk factors, including body mass index, anxiety sensitivity (AS), emotional intelligence, personality, obsessive-compulsive behavior, and coping, validated questionnaires were used. A set of univariate and multivariate logistic regression analyses were conducted. Of the variables showing significant links with CWP in the univariate individual-level analyses, including age, AS, and emotional intelligence, only emotional intelligence turned out to an independent predictor to the pathogenesis of CWP in both the individual level and discordant MZ analyses. These data indicate that in women having identical genetic risk, emotional intelligence seems to play a key role, although of small effect, in the development and/or maintenance of CWP. It further seems that many of the previously reported risk factors for CWP suffer from genetic confounding.

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Twins reared apart provide a fascinating experiment to distinguish genetic from environmental influences. However, there is as yet no broad report on distribution of twins reared apart, especially in the Chinese population. In this study, information on 18,295 volunteer twin pairs of all age groups was compiled in nine provinces or cities of China, and questionnaires were used for zygosity determination. It was discovered that twins reared apart from 0 to 10 years of age accounted for 2.2% of all twin interviewees, with the proportion of this 0–10 group separated before 1, 2, and 5 years old, accounting for 65.3%, 76.1%, and 91.3%, respectively. The proportion of twins reared apart is not significantly related to zygosity or gender, but it is related to region and twin age. As the age of twins lowers, the proportion of those reared apart gradually decreases. Twins reared apart will become rarer in the future and therefore should be cherished as a resource.

Highlights from a conference, ‘Healthier Kids: Insights From Twin Research’, held in Melbourne, Australia on December 5, 2014, are summarized. In addition to informative and exciting presentations and discussions of recent findings, three key themes emerged: (1) results from twin research have important implications for non-twins, (2) researchers from diverse disciplines should be encouraged to participate actively in twin research, and (3) investigators, twins and families need to work more collaboratively. Next, papers and studies concerning the biological bases of monozygotic (MZ) twinning, gestational diabetes and post-partum depression are reviewed. Finally, general interest reports of rare quadruplets, mistaken identity, prenatal laser surgery and a royal twin birth are provided.

Dr John MacMillan, Senior Staff Specialist at Genetic Health Queensland and Associate Professor of Medicine at The University of Queensland, passed away on December 21, 2014, aged 55 years. John was founding director at Genetic Health Queensland and was well known for his research contribution into the genetic basis of neurological disease.