Genetic Influences on Individual Differences in Exercise Behavior during Adolescence

The aim of this study was to investigate the degree to which genetic and environmental influences affect variation in adolescent exercise behavior. Data on regular leisure time exercise activities were analyzed in 8,355 adolescent twins, from three-age cohorts (13-14, 15-16, and 17–19 years). Exercise behavior was assessed with survey items about type of regular leisure time exercise, frequency, and duration of the activities. Participants were classified as sedentary, regular exercisers, or vigorous exercisers. The prevalence of moderate exercise behavior declined from age 13 to 19 years with a parallel increase in prevalence of sedentary behavior, whereas the prevalence of vigorous exercise behavior remained constant across age cohorts. Variation in exercise behavior was analyzed with genetic structural equation modeling employing a liability threshold model. Variation was largely accounted for by genetic factors (72% to 85% of the variance was explained by genetic factors), whereas shared environmental factors only accounted for a substantial part of the variation in girls aged 13-14 years (46%). We hypothesize that genetic effects on exercise ability may explain the high heritability of exercise behavior in this phase of life

Genetic correlation of exercise with heart rate and respiratory sinus arrhythmia

Purpose: A twin design was used to test whether the association between exercise behavior and heart rate and the association between exercise behavior and respiratory sinus arrhythmia (RSA) derive from a common genetic factor. Methods: Data were available from 157 adolescent (aged 13-22) and 208 middle-aged twin pairs (aged 35-62), divided into five sex by zygosity groups (male and female monozygotic twin pairs, and dizygotic twin pairs of same or opposite sex). Exercise behavior was assessed as the average weekly METs spent on sports activities or other vigorous activities in leisure time (sportMETS) in the last 3 months. RSA and heart period (HP) were assessed in the time domain from the combined ECG and respiration signals. Results: Heritability estimates were 16% and 29% for RSA, 64% and 68% for HP, and 79% and 41% for sportMETS in young and middle-aged twins, respectively. A significant association was found between RSA and sportMETS (0.17) in the adolescent twins that derived entirely from a common genetic factor. No association was found between sportMETS and RSA in the older twins. A significant association was found between HP and sportMETS in both adolescent (0.35) and middle-aged (0.18) twins. A large contribution of common genetic factors to these associations was found amounting to 84% and 88% in the young and middle-aged twins, respectively. Conclusions: Although the results of this study do not preclude causal effects of exercise on RSA and heart rate, they show that the association between exercise and these cardiovascular risk factors largely derives from a common genetic factor

Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition

Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities. Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance. Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019. Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort. Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks. Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders

Conditional accuracy in response interference tasks: Evidence from the Eriksen flanker task and the spatial conflict task

Two well-known response interference tasks are the Eriksen flanker task and the spatial conflict task. The tasks are logically equivalent, and comparable effects of current and previous stimulus type (congruent or incongruent) have been shown with regard to reaction time (RT). Here, we investigated whether interference and sequential trial effects also had comparable effects on accuracy. We specifically tested whether these effects interacted with the speed of responding using conditional accuracy functions (CAFs). The CAFs revealed that in both tasks congruency and sequential trial effects on accuracy are found only in trials with fast responses (< 600 ms). Sequential trial effects on accuracy were weaker for the flanker task than for the spatial conflict task. In very fast trials (< 400 ms) response activation by distracting flankers led to below-chance performance in the flanker task, but response activation by incongruent spatial location did not lead to below-chance performance in the spatial conflict task. The pattern of results hints at subtle differences in processing architecture between the tasks

Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up

Peer reviewedPostprin

The association of depression and anxiety with cardiac autonomic activity:The role of confounding effects of antidepressants

Background: Depression and anxiety may unfavorably impact on cardiac autonomic dysregulation. However, it is unclear whether this relationship results from a causal effect or may be attributable to confounding factors. We tested the relationship between depression and anxiety with heart rate (HR) and heart rate variability (HRV) across a 9-year follow-up (FU) period and investigated possible confounding by antidepressant use and genetic pleiotropy. Methods: Data (no. of observations = 6,994, 65% female) were obtained from the longitudinal Netherlands Study of Depression and Anxiety, with repeated waves of data collection of HR, HRV, depression, anxiety, and antidepressant use. Summary statistics from meta-analyses of genome-wide association studies were used to derive polygenic risk scores of depression, HR, and HRV. Results: Across the 9-year FU, generalized estimating equations analyses showed that the relationship between cardiac autonomic dysregulation and depression/anxiety rendered nonsignificant after adjusting for antidepressant use. A robust association was found between antidepressant use (especially tricyclic antidepressants, selective serotonin, and noradrenalin reuptake inhibitors) and unfavorable cardiac autonomic activity across all waves. However, no evidence was found for a genetic correlation of depression with HR and HRV, indicating that confounding by genetic pleiotropy is minimal. Conclusions: Our results indicate that the association between depression/anxiety and cardiac autonomic dysregulation does not result from a causal pathway or genetic pleiotropy, and these traits might therefore not be inevitably linked. Previously reported associations were likely confounded by the use of certain classes of antidepressants

Theory and Practice in Quantitative Genetics

With the rapid advances in molecular biology, the near completion of the human genome, the development of appropriate statistical genetic methods and the availability of the necessary computing power, the identification of quantitative trait loci has now become a realistic prospect for quantitative geneticists. We briefly describe the theoretical biometrical foundations underlying quantitative genetics. These theoretical underpinnings are translated into mathematical equations that allow the assessment of the contribution of observed (using DNA samples) and unobserved (using known genetic relationships) genetic variation to population variance in quantitative traits. Several statistical models for quantitative genetic analyses are described, such as models for the classical twin design, multivariate and longitudinal genetic analyses, extended twin analyses, and linkage and association analyses. For each, we show how the theoretical biometrical model can be translated into algebraic equations that may be used to generate scripts for statistical genetic software packages, such as Mx, Lisrel, SOLAR, or MERLIN. For using the former program a web-library (available from http://www.psy.vu.nl/mxbib) has been developed of freely available scripts that can be used to conduct all genetic analyses described in this paper

Ambulatory heart rate is underestimated when measured by an ambulatory blood pressure device

Objective: To test the validity of ambulatory heart rate (HR) assessment with a cuff ambulatory blood pressure (ABP) monitor. Design: Cross-instrument comparison of HR measured intermittently by a cuff ABP monitor (SpaceLabs, Redmond, Washington, USA), with HR derived from continuous electrocardiogram (ECG) recordings (1) in a controlled laboratory experiment and (2) during long-term recording in a true naturalistic setting. Participants: Six normotensive subjects participated in the laboratory study. A total of 109 male white-collar workers underwent ambulatory monitoring, of which 30 were mildly hypertensive. Methods: Four different laboratory conditions (postures: lying, sitting, standing, walking), repeated twice, were used to assess the short-term effects of cuff inflation on the HR. To test the actual ambulatory validity, participants simultaneously wore a continuous HR recorder and the ABP monitor from early morning to late evening on 2 workdays and one non-workday. Diary and vertical accelerometery information was used to obtain periods of fixed posture and (physical) activity across which HR from both devices was compared. Results: Laboratory results showed that the ABP device reliably detected HR during blood pressure measurement, but that this HR was systematically lower than the HR directly before and after the blood pressure measurement. The ambulatory study confirmed this systematic underestimation of the ongoing HR, but additionally showed that its amount increased when subjects went from sitting to standing to light physical activity (2.9; 4.3 and 9.1 bpm (beats/min), respectively). In spite of this activity-dependent underestimation of HR, the correlation of continuous ECG and intermittent ABP-derived HR was high (median r = 0.81). Also, underestimation was not different for normotensives and mild hypertensives. Conclusions: A direct effect of cuff inflation leads to the underestimation of ongoing HR during cuff-based ABP measurement. Additional underestimation of HR occurs during periods with physical activity, probably due to behavioural freezing during blood pressure measurements. HR underestimation was not affected by hypertensive state. When its limitations are taken into account, ABP-derived ambulatory HR can be considered a reliable and valid measure. © 2001 Lippincott Williams & Wilkins

Heritability and genome-wide linkage scan of subjective happiness

Causes of individual differences in happiness, as assessed with the Subjective Happiness Scale, are investigated in a large of sample twins and siblings from the Netherlands Twin Register. Over 12,000 twins and siblings, average age 24.7 years (range 12 to 88), took part in the study. A genetic model with an age by sex design was fitted to the data with structural equation modeling in Mx. The heritability of happiness was estimated at 22% for males and 41% in females. No effect of age was observed. To identify the genomic regions contributing to this heritability, a genome-wide linkage study for happiness was conducted in sibling pairs. A subsample of 1157 offspring from 441 families was genotyped with an average of 371 micro-satellite markers per individual. Phenotype and genotype data were analyzed in MERLIN with multipoint variance component linkage analysis and age and sex as covariates. A linkage signal (logarithm of odds score 2.73, empirical p value 0.095) was obtained at the end of the long arm of chromosome 19 for marker D19S254 at 110 cM. A second suggestive linkage peak was found at the short arm of chromosome 1 (LOD of 2.37) at 153 cM, marker D1S534 (empirical p value of .209). These two regions of interest are not overlapping with the regions found for contrasting phenotypes (such as depression, which is negatively associated with happiness). Further linkage and future association studies are warranted