Hemodynamic Traits Research Articles

Abstract 18928: Phenotypic Manifestations of Polygenic Risk for Ischemic Stroke in Adults Free From Disease

Introduction: Ischemic stroke is a complex heritable disease with a substantial proportion of risk attributable to polygenic factors. Little is known about how polygenic risk for stroke may manifest as intermediate phenotypes. Hypothesis: Polygenic liability for ischemic stroke will be associated with cardiometabolic phenotypes even in young adults free from disease. Methods: Polygenic risk derived from a multi ancestry population (GIGASTROKE ~1.2 million SNPs) was applied to 454 White adults from the HERITAGE Family Study with imputed whole genome data available. Participants (mean age = 31.5 ±14.5 years, 51% female) underwent robust cardiometabolic profiling including deeply phenotyped cardiopulmonary exercise tests, body composition, lipid panels, inflammatory markers, and measures of glucose homeostasis. General linear models adjusted for age and sex were used to test the association between z-scored polygenic risk of stroke (SPRS) and 130 phenotypes. A false discovery rate of <5% was used to determine significance. Results: SPRS did not associate with demographic traits or measures of body composition. SPRS was positively associated with several blood pressure related phenotypes with the strongest association between SPRS and systolic blood pressure response to acute exercise (β=0.01, p=2.86e-05), which persisted after adjustment for resting systolic blood pressure. Additionally, 19 total phenotypes were nominally associated (p<0.05) with SPRS including multiple apoB related plasma lipid traits ( Table 1 ). Interestingly, SPRS was also inversely associated with hematocrit (β= -0.06, FDR=0.004). Conclusions: Genetic risk of ischemic stroke is associated with hemodynamic traits even in a cohort of relatively young adults free from overt cardiometabolic disease. Additionally, blood pressure response to acute exercise may represent an early manifestation of genetic liability to stroke.

Intrinsic Exercise Capacity and Mitochondrial DNA Lead to Opposing Vascular-Associated Risks.

Exercise capacity is a strong predictor of all-cause morbidity and mortality in humans. However, the associated hemodynamic traits that link this valuable indicator to its subsequent disease risks are numerable. Additionally, exercise capacity has a substantial heritable component and genome-wide screening indicates a vast amount of nuclear and mitochondrial DNA (mtDNA) markers are significantly associated with traits of physical performance. A long-term selection experiment in rats confirms a divide for cardiovascular risks between low- and high-capacity runners (LCR and HCR, respectively), equipping us with a preclinical animal model to uncover new mechanisms. Here, we evaluated the LCR and HCR rat model system for differences in vascular function at the arterial resistance level. Consistent with the known divide between health and disease, we observed that LCR rats present with resistance artery and perivascular adipose tissue dysfunction compared to HCR rats that mimic qualities important for health, including improved vascular relaxation. Uniquely, we show by generating conplastic strains, which LCR males with mtDNA of female HCR (LCR-mtHCR/Tol) present with improved vascular function. Conversely, HCR-mtLCR/Tol rats displayed indices for cardiac dysfunction. The outcome of this study suggests that the interplay between the nuclear genome and the maternally inherited mitochondrial genome with high intrinsic exercise capacity is a significant factor for improved vascular physiology, and animal models developed on an interaction between nuclear and mtDNA are valuable new tools for probing vascular risk factors in the offspring.

Ventricular vortex loss analysis due to various tricuspid valve repair techniques: an ex vivo study.

The deteriorating nature of severe functional tricuspid regurgitation (FTR) has led to the heightened interest in this pathology. However, therapies are heterogeneous and an ideal technique is uncertain. The hemodynamic impact on the cardiac chamber following therapeutic repairs has not been well studied, while its analysis could be used to predict the treatment success. In this study, the hemodynamics of the right ventricle (RV) after 1) clover edge-to-edge tricuspid repair, and 2) double orifice tricuspid repair was evaluated in three right heart models using an ex vivo pulsatile platform emulating severe FTR with the aid of stereoscopic particle image velocimetry. Although all repairs substantially reduced tricuspid regurgitant area, they resulted in a more than 50% reduction in diastolic tricuspid valve (TV) opening area. Splitting the TV orifice into multiple smaller orifices by both repairs eliminated the ring-shaped vortical structure inside the RV observed in FTR cases. Postrepair RV domain was mostly occupied with irregular vortical features and isolated vortex residuals. Moreover, vortical features varied among repair samples, indicating enhanced sensitivity of RV flow to postrepair TV morphology. Compared with clover repair, double orifice subjected the RV to enhanced swirling motions and exposed more regions to vortical motions, potentially indicating better rinsing and lower risk of mural thrombus formation. Double orifice repair increased the levels of RV mean kinetic energy and viscous energy loss than those observed in clover repair, although the impact of these on the cardiac efficiency remains unclear. These preliminary insights could be used to improve future treatment design and planning.NEW & NOTEWORTHY While clover and double orifice tricuspid repairs markedly improved leaflet coaptation, they substantially reduced diastolic tricuspid opening area. Postrepair right ventricle (RV) exhibited specific hemodynamic traits, including the loss of ring-shaped vortical structure and the enhanced sensitivity of RV flow to postrepair tricuspid valve morphology. Compared with clover technique, double orifice repair led to higher swirling motions in the RV domain, which could indicate lower risk of mural thrombus formation.

Retinal Microvasculature in Relation to Central Hemodynamics in a Flemish Population.

Arterial stiffness and wave reflection predict cardiovascular mortality and morbidity and are associated with renal microvascular disease. We hypothesized that the retinal microvascular traits might be associated with central hemodynamic properties. In 735 randomly recruited Flemish (mean age, 50.3 years; 47.1% women), we derived central pulse pressure and carotid-femoral pulse wave velocity by applanation tonometry and calculated forward (Pf) and backward (Pb) pulse waves, using an automated pressure-based wave separation algorithm. We measured central retinal arteriolar (CRAE) and venular equivalent and their ratio, using IVAN software (Vasculomatic ala Nicola, version 1.1). Mean values for pulse wave velocity (n=554), Pf and Pb were 7.50 m/s, 32.0 mm Hg, and 21.5 mm Hg, respectively. In multivariable-adjusted analyses, CRAE was 4.62 µm and 1.26 µm smaller (P≤0.034) for a 1-SD increment in central mean arterial pressure (+11.3 mm Hg) and central pulse pressure (+15.2 mm Hg); a 1-SD increment in the augmentation ratio (+7.0%), aortic pulse wave velocity (+1.66 m/s), Pf (+10.0 mm Hg), and Pb (+8.5 mm Hg), was associated with smaller CRAE; the association sizes were -1.91 µm, -1.59 µm, -1.45 µm, and -2.38 µm (P≤0.014), respectively. Associations of arteriole-to-venule diameter ratio with the central hemodynamic traits mirrored those of CRAE. None of the multivariable-adjusted associations of central retinal venular diameter with the central hemodynamic traits reached significance with the exception of central diastolic blood pressure (-1.62 µm; P=0.030). In conclusion, in the general population, higher central pulse pressure, pulse wave velocity, Pf, and Pb were associated with smaller CRAE.

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality.

BackgroundDiabetes mellitus is linked to premature mortality of virtually all causes. Furin is a proprotein convertase broadly involved in the maintenance of cellular homeostasis; however, little is known about its role in the development of diabetes mellitus and risk of premature mortality.ObjectivesTo test if fasting plasma concentration of furin is associated with the development of diabetes mellitus and mortality.MethodsOvernight fasted plasma furin levels were measured at baseline examination in 4678 individuals from the population‐based prospective Malmö Diet and Cancer Study. We studied the relation of plasma furin levels with metabolic and hemodynamic traits. We used multivariable Cox proportional hazards models to investigate the association between baseline plasma furin levels and incidence of diabetes mellitus and mortality during 21.3–21.7 years follow‐up.ResultsAn association was observed between quartiles of furin concentration at baseline and body mass index, blood pressure and plasma concentration of glucose, insulin, LDL and HDL cholesterol (|0.11| ≤ β ≤ |0.31|, P < 0.001). Plasma furin (hazard ratio [HR] per one standard deviation increment of furin) was predictive of future diabetes mellitus (727 events; HR = 1.24, CI = 1.14–1.36, P < 0.001) after adjustment for age, sex, body mass index, systolic and diastolic blood pressure, use of antihypertensive treatment, alcohol intake and fasting plasma level of glucose, insulin and lipoproteins cholesterol. Furin was also independently related to the risk of all‐cause mortality (1229 events; HR = 1.12, CI = 1.05–1.19, P = 0.001) after full multivariable adjustment.ConclusionIndividuals with high plasma furin concentration have a pronounced dysmetabolic phenotype and elevated risk of diabetes mellitus and premature mortality.

Abstract 121: Longitudinal Associations of Childhood Hemodynamic and Metabolic Traits to Adult Aortic Stiffness Vary by Race: The Bogalusa Heart Study

Background: Aortic stiffness predicts future hypertension and cardiovascular disease (CVD) events. CVD predictors like metabolic traits and arterial stiffness vary by race. We hypothesized that in longitudinal analyses, metabolic traits since childhood would be associated with adulthood aortic stiffness, and that these associations vary by race in the biracial (black vs. white) Bogalusa Heart Study cohort. Methods: Included participants had ultrasound as young adults for aorta-femoral pulse wave velocity (afPWV) and at least three Study visits over the life course. Sampled participants (n=1081) were 24-44 years old, 31% black, 57% female, and mean follow-up was 27 years. Demographic, anthropometric, blood pressure, lipid, glucose and tobacco exposure data were extracted from each visit. Given variable visit intervals and numbers, growth mixed models were used to compute total area under the curve for risk factors on the primary outcome of interest, young adult afPWV. Childhood versus cumulative risk factors to afPWV associations were examined with multivariable adjusted linear regression. Significant race by risk factor interaction terms (p&lt;0.001) led to race-specific reporting. Results: Adult afPWV was higher in black (5.4+/-1.2 m/s) than white (5.2+/-1.1 m/s) participants (p=0.01). Overall, afPWV was associated with childhood and cumulative low density lipoprotein cholesterol (LDL-C, β=0.13; p&lt;0.001 and β=0.08; p&lt;0.01, respectively) and mean arterial pressure (MAP, β=0.1; p=0.02 and β=0.18; p&lt;0.001) and cumulative glucose (β=0.13; p&lt;0.001). For blacks and whites, higher afPWV was associated with childhood LDL-C (β=0.17; p&lt;0.01 and β=0.1; p&lt;0.01) and cumulative glucose (β=0.14; p=0.02 and β=0.15; p&lt;0.001). Only in whites were childhood and cumulative MAP (β=0.08; p=0.04 and β=0.22; p&lt;0.001) and cumulative LDL-C (β=0.1; p&lt;0.01) associated. Conclusions: Young adult aortic stiffness was associated with childhood metabolic and hemodynamic traits even after accounting for cumulative levels of these traits. The associations appear to vary by race and by child versus adult life stage. Future work may examine the mechanisms of these race-specific differences and implications for CVD event risk.

Advances in Exercise, Fitness, and Performance Genomics in 2015.

This review of the exercise genomics literature encompasses the highest-quality articles published in 2015 across seven broad topics: physical activity behavior, muscular strength and power, cardiorespiratory fitness and endurance performance, body weight and adiposity, insulin and glucose metabolism, lipid and lipoprotein metabolism, and hemodynamic traits. One study used a quantitative trait locus for wheel running in mice to identify single nucleotide polymorphisms (SNPs) in humans associated with physical activity levels. Two studies examined the association of candidate gene ACTN3 R577X genotype on muscular performance. Several studies examined gene-physical activity interactions on cardiometabolic traits. One study showed that physical inactivity exacerbated the body mass index (BMI)-increasing effect of an FTO SNP but only in individuals of European ancestry, whereas another showed that high-density lipoprotein cholesterol (HDL-C) SNPs from genome-wide association studies exerted a smaller effect in active individuals. Increased levels of moderate-to-vigorous-intensity physical activity were associated with higher Matsuda insulin sensitivity index in PPARG Ala12 carriers but not Pro12 homozygotes. One study combined genome-wide and transcriptome-wide profiling to identify genes and SNPs associated with the response of triglycerides (TG) to exercise training. The genome-wide association study results showed that four SNPs accounted for all of the heritability of △TG, whereas the baseline expression of 11 genes predicted 27% of △TG. A composite SNP score based on the top eight SNPs derived from the genomic and transcriptomic analyses was the strongest predictor of ΔTG, explaining 14% of the variance. The review concludes with a discussion of a conceptual framework defining some of the critical conditions for exercise genomics studies and highlights the importance of the recently launched National Institutes of Health Common Fund program titled "Molecular Transducers of Physical Activity in Humans."

Multiple metabolic genetic risk scores and type 2 diabetes risk in three racial/ethnic groups.

CONTEXT/RATIONALE: Meta-analyses of genome-wide association studies have identified many single-nucleotide polymorphisms associated with various metabolic and cardiovascular traits, offering us the opportunity to learn about and capitalize on the links between cardiometabolic traits and type 2 diabetes (T2D). In multiple datasets comprising over 30 000 individuals and 3 ethnic/racial groups, we calculated 17 genetic risk scores (GRSs) for glycemic, anthropometric, lipid, hemodynamic, and other traits, based on the results of recent trait-specific meta-analyses of genome-wide association studies, and examined associations with T2D risk. Using a training-testing procedure, we evaluated whether additional GRSs could contribute to risk prediction. In European Americans, we find that GRSs for T2D, fasting glucose, fasting insulin, and body mass index are associated with T2D risk. In African Americans, GRSs for T2D, fasting insulin, and waist-to-hip ratio are associated with T2D. In Hispanic Americans, GRSs for T2D and body mass index are associated with T2D. We observed a trend among European Americans suggesting that genetic risk for hyperlipidemia is inversely associated with T2D risk. The use of additional GRSs resulted in only small changes in prediction accuracy in multiple independent validation datasets. The analysis of multiple GRSs can shed light on T2D etiology and how it varies across ethnic/racial groups. Our findings using multiple GRSs are consistent with what is known about the differences in T2D pathogenesis across racial/ethnic groups. However, further work is needed to understand the putative inverse correlation of genetic risk for hyperlipidemia and T2D risk and to develop ethnic-specific GRSs.

Folate Deficiency Is Associated With Oxidative Stress, Increased Blood Pressure, and Insulin Resistance in Spontaneously Hypertensive Rats

The role of folate deficiency and associated hyperhomocysteinemia in the pathogenesis of metabolic syndrome is not fully established. In the current study, we analyzed the role of folate deficiency in pathogenesis of the metabolic syndrome in the spontaneously hypertensive rat (SHR). Metabolic and hemodynamic traits were assessed in SHR/Ola rats fed either folate-deficient or control diet for 4 weeks starting at the age of 3 months. Compared to SHRs fed a folate-replete diet, SHRs fed a folate-deficient diet showed significantly reduced serum folate (104 ± 5 vs. 11 ± 1 nmol/L, P < 0.0005) and urinary folate excretion (4.3 ± 0.6 vs. 1.2 ± 0.1 nmol/16 h, P < 0.0005) together with a near 3-fold increase in plasma total homocysteine concentration (4.5 ± 0.1 vs 13.1 ± 0.7 μmol/L, P < 0.0005), ectopic fat accumulation in liver, and impaired glucose tolerance. Folate deficiency also increased systolic blood pressure by approximately 15 mm Hg (P < 0.01). In addition, the low-folate diet was accompanied by significantly reduced activity of antioxidant enzymes and increased concentrations of lipoperoxidation products in liver, renal cortex, and heart. These findings demonstrate that the SHR model is susceptible to the adverse metabolic and hemodynamic effects of low dietary intake of folate. The results are consistent with the hypothesis that folate deficiency can promote oxidative stress and multiple features of the metabolic syndrome that are associated with increased risk for diabetes and cardiovascular disease.

Autonomic and Hemodynamic Origins of Pre-Hypertension: Central Role of Heredity

The purpose of this study is to better understand the origins and progression of pre-hypertension.Pre-hypertension is a risk factor for progression to hypertension, cardiovascular disease, and increased mortality. We used a cross-sectional twin study design to examine the role of heredity in likely pathophysiological events (autonomic or hemodynamic) in pre-hypertension.Eight hundred twelve individuals (337 normotensive, 340 pre-hypertensive, 135 hypertensive) were evaluated in a sample of twin pairs, their siblings, and other family members. They underwent noninvasive hemodynamic, autonomic, and biochemical testing, as well as estimates of trait heritability (the percentage of trait variance accounted for by heredity) and pleiotropy (the genetic covariance or shared genetic determination of traits) by variance components.In the hemodynamic realm, an elevation of cardiac contractility prompted increased stroke volume, in turn increasing cardiac output, which elevated blood pressure into the pre-hypertension range. Autonomic monitoring detected an elevation of norepinephrine secretion plus a decline in cardiac parasympathetic tone. Twin pair variance components documented substantial heritability as well as joint genetic determination for blood pressure and the contributory autonomic and hemodynamic traits. Genetic variation at a pathway locus also indicated pleiotropic effects on contractility and blood pressure.Elevated blood pressure in pre-hypertension results from increased cardiac output, driven by contractility as well as heart rate, which may reflect both diminished parasympathetic and increased sympathetic tone. In the face of increased cardiac output, systemic vascular resistance fails to decline homeostatically. Such traits display substantial heritability and shared genetic determination, although by loci not yet elucidated. These findings clarify the role of heredity in the origin of pre-hypertension and its autonomic and hemodynamic pathogenesis. The results also establish pathways that suggest new therapeutic targets for pre-hypertension, or approaches to its prevention.

A combinatorial genetic approach identifies a significant locus that controls elevated heart rate in mice

Elevated heart rate (HR) is a risk factor for cardiovascular diseases. The goal of the study was to use a combination of quantitative trait locus (QTL) and genome‐wide association studies (GWAS) to map hemodynamic traits in mice. QTL analyses were performed in a C3HeBxSJL backcross (n=134). GWAS were done using the hybrid mouse diversity panel (HMDP; 30 inbred strains). HR and systolic blood pressure (SBP) were measured by the tail cuff method. HR was approximately 80 beats/min higher in SJL compared to C3HeB. There was a significant distribution of the HR (536–763 beats/min) in N2 mice. We discovered a highly significant QTL (LOD=6.7, p&lt;0.001) on chromosome 7 (41cM) for HR in the C3HeBxSJL backcross. In the HMDP (n=5–6/strain) we found that HR (beats/min) ranged from 546±12 in C58/J strain to 717±7 in MA/MyJ mice. SBP (mmHg) ranged from 99±6 in I/LnJ to 149±2 in SWR/J mice. GWAS for HR recognized over 100 significant loci (‐log[p‐value]≥6). We found fourteen SNPs that are localized within 10 known genes. Importantly, a significant locus on mouse chromosome 7 co‐localized with the QTL for elevated HR found in the C3HeBxSJL backcross. GWAS for SBP identified two SNPs on chromosome 16. In summary, we used a combined genetic approach to identify a novel elevated heart rate locus on mouse chromosome 7. This study was supported by Russian Federation Program #2011‐1.5‐501‐006‐ 024 and NIH HL105623 (VAK); NIH HL30568 and HL42488 (AJL)

Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse

Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58 000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures. Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives. Genetic mappings uncovered numerous shared genes among substance use, stress response, obesity and hemodynamic traits, including CAMK4, CNTN4, DLG2, FHIT, GRID2, ITPR2, NOVA1 and PRKCE, forming network of interacting proteins, sharing synaptic function and display higher and patterned expression profiles in brain-related tissues; moreover, pathway analysis of shared genes pointed to long-term potentiation. Subgroup genetic mappings uncovered additional shared synaptic genes, including CAMK4, CNTN5 and DNM3 (hypertension-specific); CNTN4, DNM3, FHIT and ITPR1 (sex-specific), having protein interactions with genes driven from general analysis. In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences.

Heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs

Endurance training-induced changes in hemodynamic traits are heritable. However, few genes associated with heart rate training responses have been identified. The purpose of our study was to perform a genome-wide association study to uncover DNA sequence variants associated with submaximal exercise heart rate training responses in the HERITAGE Family Study. Heart rate was measured during steady-state exercise at 50 W (HR50) on 2 separate days before and after a 20-wk endurance training program in 483 white subjects from 99 families. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using the Illumina BeadStation 500GX platform. After quality control procedures, 320,000 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study analyses, which were performed using the MERLIN software package (single-SNP analyses and conditional heritability tests) and standard regression models (multivariate analyses). The strongest associations for HR50 training response adjusted for age, sex, body mass index, and baseline HR50 were detected with SNPs at the YWHAQ locus on chromosome 2p25 (P = 8.1 × 10(-7)), the RBPMS locus on chromosome 8p12 (P = 3.8 × 10(-6)), and the CREB1 locus on chromosome 2q34 (P = 1.6 × 10(-5)). In addition, 37 other SNPs showed P values <9.9 × 10(-5). After removal of redundant SNPs, the 10 most significant SNPs explained 35.9% of the ΔHR50 variance in a multivariate regression model. Conditional heritability tests showed that nine of these SNPs (all intragenic) accounted for 100% of the ΔHR50 heritability. Our results indicate that SNPs in nine genes related to cardiomyocyte and neuronal functions, as well as cardiac memory formation, fully account for the heritability of the submaximal heart rate training response.

Renal Albumin Excretion

Albumin excretion marks early glomerular injury in hypertension. This study investigated heritability of albumin excretion in twin pairs and its genetic determination by adrenergic pathway polymorphism. Genetic associations used single nucleotide polymorphisms at adrenergic pathway loci spanning catecholamine biosynthesis, storage, catabolism, receptor action, and postreceptor signal transduction. We studied 134 single nucleotide polymorphisms at 46 loci for a total of >51,000 genotypes. Albumin excretion heritability was 45.2+/-7.4% (P=2x10(-7)), and the phenotype aggregated significantly with adrenergic, renal, metabolic, and hemodynamic traits. In the adrenergic system, excretions of both norepinephrine and epinephrine correlated with albumin. In the kidney, albumin excretion correlated with glomerular and tubular traits (Na(+) and K(+) excretion; fractional excretion of Na(+) and Li(+)). Albumin excretion shared genetic determination (genetic covariance) with epinephrine excretion, and environmental determination with glomerular filtration rate and electrolyte intake/excretion. Albumin excretion associated with polymorphisms at multiple points in the adrenergic pathway: catecholamine biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention, diagnosis, and treatment.

The human gene map for performance and health-related fitness phenotypes.

The aim of this paper is to describe the first human gene map for physical performance and health-related fitness traits based on the papers published until the end of 2000. Studies of candidate genes using case-control and other designs are reviewed. Quantitative trait loci from the limited evidence reported to date in genomic scans are also incorporated. Performance and fitness phenotypes in the sedentary state as well as their changes during exercise, if applicable, or in response to exercise training are considered. Physical performance traits include cardiorespiratory endurance indicators and muscular strength or muscular performance variables. Health-related fitness phenotypes are grouped under the following categories: hemodynamic traits; anthropometry and body composition; insulin and glucose metabolism; and lipids, lipoproteins, and hemostatic factors. A yearly update of this human gene map will be published.