Decreased Walking Ability

Introduction

Walking is a fundamental human activity, crucial for daily life, independence, and overall health. The ability to walk, and particularly an individual’s usual walking pace, serves as a significant indicator of physical function and general well-being. A decreased walking ability or a slower self-reported walking pace is often associated with various health concerns and can impact an individual’s quality of life.

Biological Basis

Research, including genome-wide association studies (GWAS), has demonstrated that walking pace has a notable genetic component. The SNP-heritability for self-reported walking pace is estimated at 13.2% on the liability scale, indicating a modest genetic influence.^[1]This heritability is reduced to 8.9% when Body Mass Index (BMI) is accounted for, suggesting that BMI mediates some of the genetic effects on walking pace, though a substantial portion remains independent.^[1] GWAS have identified 70 independent genetic loci associated with self-reported walking pace.^[1] Key implicated genes include SLC39A8, which has links to metabolic traits; FTO, strongly associated with fat mass and obesity; andTCF4, related to neurocognitive traits and psychiatric conditions.^[1] Tissue-specific enrichments for these genetic signals have been observed in brain regions such as the cerebellar hemisphere and cerebellum, highlighting the neurological underpinnings of walking ability.^[1]Genetic analysis also reveals significant overlaps between walking pace and other complex traits. These include strong genetic correlations with anthropometric traits (e.g., BMI), cardiometabolic traits, cognitive abilities (e.g., years of schooling, intelligence), longevity, lung function, muscular strength (e.g., hand grip strength), and psychiatric traits (e.g., insomnia, depressive symptoms).^[1] Many of these genetic correlations persist even after adjusting for BMI, suggesting shared biological mechanisms beyond weight.^[1]

Clinical Relevance

Walking pace is a powerful predictor of health outcomes and survival. Studies indicate a strong association between brisk walking and beneficial effects on health and survival.^[1]Conversely, a decreased walking ability or slow walking pace can be an early clinical sign or symptom of underlying health issues, age-related decline, or specific conditions. For instance, difficulties with walking are a recognized subphenotype in diseases like Charcot-Marie-Tooth Disease Type 1A, where disease severity often increases with age.^[2] Monitoring changes in walking ability can therefore be a valuable tool in clinical assessments for identifying individuals at risk for various diseases, including cardiometabolic conditions, and for tracking overall health status.

Social Importance

The ability to walk effectively is paramount for maintaining independence, participating in social activities, and ensuring a good quality of life throughout the lifespan. A decline in walking ability can lead to reduced physical activity, social isolation, and increased risk of falls, significantly impacting an individual’s autonomy. From a public health perspective, understanding the genetic and environmental factors influencing walking pace is crucial for developing strategies to promote physical activity and healthy aging. Identifying individuals genetically predisposed to a slower walking pace could allow for targeted interventions aimed at improving mobility and overall health.

Phenotype Definition and Measurement Challenges

The primary phenotype, self-reported walking pace, is an ordinal categorical variable (slow, steady/average, brisk).^[1] While this provides ease of measurement and utility in large cohorts, it is a subjective measure that contrasts with objective walking pace measurements obtained under controlled conditions, potentially limiting the precision and accuracy of the phenotype’s assessment.^[1] Analyzing these ordered categories on a linear scale, as was done, introduces strong assumptions about the uniform distances between categories, which can complicate the interpretation of SNP effect sizes, SNP-heritability, and causal effect estimates.^[1]Furthermore, the absence of detailed questionnaire data on the specific context of walking behavior (e.g., for exercise, travel, or leisure) means that the reported genetic associations may not hold for more specific measures of gait, requiring further investigation into the generalizability of these findings to interventions aimed at increasing objectively assessed walking pace.^[1]

Methodological Constraints and Replication Challenges

The computational demands of applying advanced ordinal logistic regression methods to densely imputed GWAS datasets at the UK Biobank scale necessitated alternative analytical approaches, such as the use of a linear mixed model, which introduces inherent assumptions regarding the ordinal nature of the trait.^[1] A significant limitation is the tentative nature of the associated loci, which require validation in independent cohorts; the inability to obtain relevant data from other prospective studies during the research period hindered this crucial replication step.^[1] Moreover, Mendelian Randomization (MR) analyses, while powerful, rely on a number of assumptions to infer causality, and the specific biological and psychological mechanisms underlying self-reported walking pace remain unclear, potentially impacting the validity of MR results.^[1] The analyses also faced limited statistical power in certain multivariable MR settings, particularly in accurately detecting both direct and indirect causal effects, which can lead to an underestimation of complex genetic pathways or an increased risk of false positives.^[1]

Generalizability, Confounding, and Unexplained Variance

The study population, comprising primarily individuals of European ancestry from the UK Biobank, restricts the generalizability of the findings to other ancestral populations, as genetic architectures and environmental exposures can vary substantially across different ethnic groups.^{[1], [3], [4]} This demographic homogeneity may contribute to “hidden heritability” due to uncaptured heterogeneity across diverse populations. The estimated SNP-heritability of self-reported walking pace was modest at 13.2% on the liability scale, indicating that a substantial portion of the variance is likely influenced by environmental factors or complex gene-environment interactions, suggesting the trait is largely modifiable.^[1] Furthermore, the strong genetic correlation and observed pleiotropic effects with other traits, particularly BMI, present a confounding challenge; a significant number of the initial genetic loci lost genome-wide significance after adjusting for BMI, suggesting that many associations might be mediated through or confounded by adiposity-related pathways.^[1]

Variants

The gene LITAF (Lipopolysaccharide-Induced TNF-alpha Factor) plays a crucial role in immune responses, particularly in regulating inflammation and programmed cell death. LITAFis involved in the cellular response to stress and infection, influencing the production of inflammatory cytokines like TNF-alpha. A common genetic variation,rs8046213 , located within or near the LITAFgene, may subtly alter its expression or the function of the protein it encodes. Such alterations could impact the body’s inflammatory pathways and cellular health, which are vital for maintaining neurological integrity and muscle function. Indeed, dysfunction in these areas can contribute to conditions that impair walking ability, such as Charcot-Marie-Tooth disease type 1A (CMT1A), a hereditary neuropathy that leads to muscle weakness and atrophy, directly affecting mobility.^[2]The broader genetic landscape influencing walking ability is complex, involving genes that regulate diverse biological processes, from neurological development to muscle function and inflammatory responses. For instance, whileLITAF influences inflammation, other genetic variants, such as those near LINC00243, have been identified as suggestive modifiers in CMT1A, influencing symptoms like difficulties with eating and hearing loss, which are indicative of widespread neurological impact.^[2] Similarly, genes like MYO18B, which is highly expressed in skeletal muscle and heart, are implicated in cognitive functions such as mathematical abilities and brain structural variations, highlighting the intricate connections between brain health, muscle function, and overall motor control.^[5] Variants in axon guidance receptors like ROBO2 (e.g., rs7642482 ) are also linked to early expressive vocabulary, underscoring how genetic factors in neurological development can broadly influence motor and cognitive skills.^[6] Self-reported walking pace is a highly heritable trait, with genetic factors accounting for approximately 13.2% of its variation on the liability scale, suggesting a significant genetic component underlying this aspect of physical function.^[1]Genetic studies have revealed strong correlations between walking pace and other important health indicators, including body mass index (BMI), educational attainment, intelligence, and longevity, implying shared biological mechanisms that influence overall health and physical performance.^[1] Specific intergenic variants, such as rs34898535 and rs11881338 , have been associated with self-reported walking pace, indicating that numerous genetic loci contribute to this complex trait.^[1] Furthermore, certain brain regions, notably the cerebellar hemisphere and cerebellum, which are critical for motor coordination and balance, show enriched gene expression patterns associated with walking pace, reinforcing the neurological basis of this essential human ability.^[1]

Key Variants

RS ID	Gene	Related Traits
rs8046213	LITAF	decreased walking ability

Defining Walking Ability and Its Measurement

Walking ability, specifically as “self-reported walking pace,” is precisely defined and operationalized based on perceived speed. Individuals categorize their usual walking pace into distinct levels: “slow,” “steady/average,” or “brisk”.^[1] These categories are given operational definitions with specific speed thresholds: a slow pace is considered less than 3 miles per hour, a steady/average pace falls between 3 and 4 miles per hour, and a brisk pace exceeds 4 miles per hour.^[1] This trait is typically ascertained through self-report, such as via a touchscreen questionnaire, which asks individuals to describe their usual walking speed.^[1] Conceptually, self-reported walking pace is viewed as a general indicator of an individual’s perceived health, reflecting underlying genetic and environmental factors that influence this self-perception.^[1] While distinct from objectively measured walking pace, it provides a readily accessible and interpretable measure.

Categorization, Classification, and Underlying Models

The classification of walking ability primarily employs a categorical system, where individuals are assigned to one of three ordered categories: slow, steady/average, or brisk.^[1] For quantitative analysis, these categories are typically coded numerically, such as 0 for slow, 1 for steady/average, and 2 for brisk walking pace.^[1] While initially an observed categorical variable, genetic analyses often convert this phenotype to an underlying “liability scale,” which models self-reported walking pace as a continuous trait.^[1] This dimensional approach allows for more interpretable estimates of heritability, accounting for the genetic and environmental factors that influence an individual’s placement within these perceived categories. The methodology acknowledges the challenges of analyzing ordered categorical variables on a linear scale, contrasting it with more complex ordinal logistic regression methods.^[1]

Associated Traits, Genetic Markers, and Clinical Relevance

The terminology surrounding walking ability extends to its numerous health correlates, highlighting its broad clinical significance. “Self-reported walking pace” is genetically correlated with a wide array of anthropometric, cardiometabolic, respiratory, psychiatric, and cognitive traits.^[1]Key terms include associations with lower Body Mass Index (BMI), reduced risk of coronary artery disease, higher HDL cholesterol levels, improved lung function (e.g., FEV1), increased years of schooling, greater intelligence, and fewer depressive symptoms.^[1] Specific genetic loci identified as potential biomarkers include regions within SLC39A8, FTO, and TCF4.^[1] While some genetic associations with walking pace are mediated by BMI, a substantial component of its genetic architecture is independent of BMI, underscoring its multifaceted biological and psychological underpinnings.^[1]

Causes of Decreased Walking Ability

Decreased walking ability is a complex trait influenced by a combination of genetic predispositions, environmental factors, the interplay between them, and the cumulative effects of aging and health conditions. Understanding these various causal pathways provides a comprehensive view of how an individual’s capacity for walking can be diminished.

Genetic Foundations of Walking Ability

Walking ability has a significant genetic component, characterized by its polygenic nature, where many genetic variants collectively contribute to an individual’s walking pace. Studies on self-reported walking pace estimate its SNP-heritability at approximately 13.2% on the liability scale, indicating that inherited genetic variations play a role in determining an individual’s propensity for a certain walking pace.^[1]This trait is influenced by a large number of genes, each with a small effect. Genome-wide association studies have identified 144 independent significant single nucleotide polymorphisms (SNPs) across 70 genomic loci associated with walking pace.^[1] Further analyses have linked these loci to 535 genes through positional and expression quantitative trait loci (eQTL) mapping, with tissue-specific enrichments observed in the cerebellar hemisphere and cerebellum, suggesting a neurological basis for gait regulation.^[1] The genetic architecture of walking ability shows extensive overlap with numerous other complex traits, reflecting shared biological mechanisms or causal pathways.^[1]Significant genetic correlations have been observed with anthropometric traits like Body Mass Index (BMI), educational attainment (years of schooling), intelligence, and longevity (parents’ age at death), indicating a multifaceted genetic influence.^[1]For instance, 28 loci associated with walking pace are also linked to BMI, while 20 overlap with educational attainment and 13 with hand grip strength.^[1]Beyond this polygenic influence, specific Mendelian genetic disorders, such as Charcot-Marie-Tooth Disease Type 1A (CMT1A) caused by a duplication on chromosome 17p, directly result in decreased walking ability through neurological impairment, highlighting severe, single-gene or chromosomal effects.^[2]

Interplay of Lifestyle, Environment, and Health Conditions

Environmental and lifestyle factors significantly modulate walking ability, often interacting with genetic predispositions. While walking pace has an inherited component, its “largely modifiable” nature underscores the profound impact of lifestyle choices, including diet, physical activity levels, and exposure to various environmental influences.^[1] A key example of gene-environment interaction is the relationship with BMI; genetic associations with walking pace are often attenuated when BMI is included as a covariate, suggesting that BMI can mediate the causal pathway between genotype and walking pace.^[1]This implies that while an individual might be genetically predisposed to a slower pace, environmental factors contributing to higher BMI can further exacerbate this tendency, or conversely, a healthy lifestyle can mitigate it.

Decreased walking ability is frequently a consequence or a reflection of underlying health conditions and comorbidities. Genetic correlation analyses reveal significant overlaps between walking pace and various cardiometabolic traits and diseases, including coronary heart disease, type 2 diabetes, and altered lipid levels.^[1]Respiratory traits, such as lung function measures (e.g., forced vital capacity and forced expiratory volume in 1 second), and psychiatric conditions like depressive symptoms and insomnia, also show strong genetic correlations with walking pace, even after accounting for BMI.^[1] These comorbidities, whether genetically linked or arising from environmental influences, contribute directly to reduced mobility by affecting cardiorespiratory fitness, muscular strength, and overall physical and mental well-being.^[1]

Developmental Trajectories and Age-Related Changes

Early life influences and developmental trajectories likely play a role in establishing an individual’s baseline walking ability and its susceptibility to decline. Although specific epigenetic mechanisms such as DNA methylation or histone modifications are not detailed in the available research, the genetic architecture of walking pace, intertwined with traits like birth weight and educational attainment, suggests that factors influencing early development can set a foundation for later-life mobility and cognitive function.^[1] These early-life factors, potentially mediated by gene-environment interactions during critical developmental windows, could shape neuromuscular development and overall physical capacity, impacting walking ability throughout life.

Aging is a prominent factor contributing to decreased walking ability, often through a combination of physiological changes and accumulated health conditions. Walking pace, along with proxies for overall muscle strength like hand grip strength, is known to decline with age.^[1]The genetic correlation between walking pace and parents’ age at death, a measure of longevity, further underscores the link between genetic factors influencing aging processes and sustained mobility.^[1]This age-related decline is not solely due to chronological age but is also influenced by the accumulation of comorbidities, reduced physical activity, and progressive neurological and musculoskeletal changes that impair gait and balance.^[1]

Biological Background

Decreased walking ability, or slower walking pace, is a complex trait influenced by a multitude of interconnected biological systems, ranging from genetic predispositions to molecular and cellular functions, and extending to the integrated physiology of tissues and organs. While walking pace is largely modifiable, genetic factors contribute to its variability, with a estimated SNP-heritability of 13.2% on the liability scale.^[1]Understanding the underlying biological mechanisms is crucial for comprehending its implications for overall health and disease.

Genetic Underpinnings and Molecular Pathways of Locomotion

The genetic architecture of walking ability involves numerous loci and genes that influence various biological processes. A genome-wide association study identified 70 independent genomic loci associated with self-reported walking pace, with 535 genes implicated through positional and expression quantitative trait loci (eQTL) mapping . This involves complex signaling cascades within neuronal networks that regulate motor cortex activity, basal ganglia function, and cerebellar coordination, ultimately impacting the efficiency and speed of gait. The observed genetic overlap between walking pace, increased years of education, and greater intelligence further underscores the role of higher cognitive functions, such as motivation and self-management, in maintaining optimal physical activity levels throughout life.^[1]Furthermore, genetic correlations with muscular strength, specifically hand grip strength, highlight the essential contribution of the musculoskeletal system, where gene regulation affects muscle fiber type, contractile protein expression, and neuromuscular junction integrity, directly impacting the force generation required for locomotion.^[1]

Metabolic and Bioenergetic Regulation

Metabolic pathways play a pivotal role in sustaining walking ability by governing energy production and substrate utilization. Genetic associations with SLC39A8on chromosome 4, a gene previously linked to metabolic traits, indicate that the transport and metabolism of essential nutrients are critical for cellular function, particularly in energy-demanding tissues like muscle and brain.^[1] Similarly, the FTOgene on chromosome 16, strongly associated with fat mass and obesity, highlights the impact of energy storage and expenditure on walking pace, where altered metabolic regulation can lead to increased body mass and reduced physical efficiency.^[1]These genetic predispositions influence various metabolic processes, including glucose uptake, lipid oxidation, and mitochondrial respiration, which are crucial for generating ATP to fuel muscle contraction and neural activity. Dysregulation in these metabolic pathways, such as those implicated in cardiometabolic conditions like type 2 diabetes and dyslipidemia, can impair muscle endurance and overall physical capacity, directly contributing to a decreased walking ability.^[1]

Integrated Physiological Networks and Pleiotropy

Walking ability is an emergent property of integrated physiological networks, with genetic influences extending across multiple bodily systems through pleiotropic effects and pathway crosstalk. Genetic correlations exist between self-reported walking pace and a wide array of traits, including respiratory function (e.g., forced vital capacity and forced expiratory volume in 1 second), psychiatric conditions (e.g., depressive symptoms and insomnia), and various cardiometabolic parameters.^[1]This suggests that certain genetic variants or regulatory mechanisms can simultaneously affect seemingly disparate biological pathways, leading to coordinated or cascading effects across organs. For example, a genetic predisposition impacting systemic inflammation or vascular health might indirectly influence both lung capacity and muscle perfusion, thereby affecting walking performance. These network interactions represent a hierarchical regulation where genetic signals propagate through complex biological systems, influencing overall physiological resilience and the capacity for physical activity.^[1]

Genetic and Environmental Modifiers of Locomotion

The genetic architecture of walking ability involves complex regulatory mechanisms, yet the phenotype remains highly modifiable, indicating significant environmental and lifestyle influences. Positional mapping and expression quantitative trait loci (eQTL) mapping have identified numerous genes, includingSLC39A8, FTO, and TCF4, whose expression levels are influenced by genetic variants, thereby affecting cellular and systemic functions relevant to walking.^[1]These regulatory mechanisms, including transcription factor binding and post-translational modifications, fine-tune gene expression and protein activity in response to both genetic instructions and environmental cues. Despite a modest genetic component, self-reported walking pace is largely modifiable, suggesting that lifestyle interventions, exercise, and behavioral adjustments can significantly impact an individual’s gait speed, even in the presence of genetic predispositions.^[1] This highlights the dynamic interaction between an individual’s genetic blueprint and their environment, where adaptive responses can compensate for certain genetic vulnerabilities or enhance inherent capacities.

Prognostic Indicator and Mortality Risk

Decreased walking ability, often reflected by a slower self-reported walking pace, serves as a significant prognostic indicator for overall health and long-term survival.^[1]Research, including large-scale genome-wide association studies, has established a strong inverse association between self-reported walking pace and all-cause mortality risk, even after accounting for factors like body mass index.^[1] This suggests that walking pace is not merely a consequence of poor health but an independent marker that can predict adverse outcomes, including increased risk of death.^[1]The genetic predisposition towards a slower walking pace further underscores its prognostic value, indicating that individuals with a genetic profile associated with decreased walking ability may inherently face a higher risk of mortality.^[1]This intrinsic link makes walking pace a valuable, easily measurable clinical marker for identifying individuals at higher risk for various health complications and for predicting disease progression, potentially guiding earlier, more targeted interventions to improve long-term patient outcomes.^[1]

Associations with Systemic Health and Comorbidities

Decreased walking ability is genetically correlated with a broad spectrum of systemic health conditions and comorbidities, highlighting its intricate connection to overall physiological function.^[1]Studies reveal significant genetic overlaps with cardiometabolic traits, such as body mass index, coronary heart disease, type 2 diabetes, and dyslipidemia.^[1]Furthermore, genetic correlations extend to respiratory function, including measures like forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1), as well as psychiatric conditions such as insomnia and depressive symptoms.^[1]A strong genetic correlation has also been observed between walking pace and hand grip strength, a recognized proxy for overall muscular strength, suggesting a shared genetic basis for age-related declines in physical function.^[1]These widespread associations, some of which persist even after adjusting for BMI, imply that decreased walking ability may be part of a broader syndromic presentation or reflect shared biological pathways influencing multiple organ systems.^[1] Understanding these genetic and phenotypic interconnections can aid in comprehensive risk assessment, identifying patients who may benefit from multidisciplinary care to address co-occurring conditions.^[1]

Potential as a Modifiable Intervention Target

Given that self-reported walking pace has a modest genetic component (estimated at 13.2% heritability on the liability scale), it is largely modifiable, presenting a significant opportunity for clinical intervention.^[1] Mendelian randomization analyses provide evidence suggesting a potential causal link where an increased walking pace is associated with a lower cardiometabolic risk profile, implying that interventions aimed at improving walking ability could yield beneficial effects across a range of health outcomes.^[1]This positions walking pace as a practical and accessible target for health promotion and disease prevention strategies in the general adult population.^[1] The ease of self-reported measurement makes walking pace a highly feasible metric for developing pragmatic, personalized interventions and monitoring their effectiveness in patient care.^[1]Clinicians can utilize walking pace as a simple diagnostic utility for risk stratification, identifying high-risk individuals who may benefit most from tailored exercise-based programs or lifestyle modifications.^[1] While further research is needed to generalize findings from self-reported pace to objectively assessed walking pace, the strong association with health outcomes supports its utility in guiding health advice and promoting active lifestyles.^[1]

Frequently Asked Questions About Decreased Walking Ability

These questions address the most important and specific aspects of decreased walking ability based on current genetic research.

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1. Why do I walk slower than my friend, even if we seem pretty similar?

Genetics play a role, accounting for about 13% of the differences in walking pace between people. Even after considering factors like weight, a significant genetic influence remains. This means some individuals are simply predisposed to a slower pace due to their unique genetic makeup and shared biological mechanisms with other traits like muscle strength or metabolism.

2. Does my family history mean I’ll definitely walk slower as I get older?

While genetics do influence walking pace, accounting for a modest portion of the variation (around 13%), it doesn’t mean it’s inevitable. Many environmental factors and lifestyle choices also play a significant role. Your genetic predisposition might make you more susceptible, but it’s largely modifiable through activity and healthy habits throughout your life.

3. Is it true that how I think affects how fast I can walk?

Yes, there’s a strong genetic overlap between walking pace and cognitive abilities like intelligence and years of schooling. Genes such asTCF4, related to neurocognitive traits, and those enriched in brain regions like the cerebellum, are linked to walking. This suggests that how your brain functions, including processing and coordination, can indeed influence your walking ability.

4. Can my diet or weight problems make my walking worse, even if I feel okay otherwise?

Absolutely. Genes strongly linked to fat mass and obesity, likeFTO, are also associated with walking pace. Your Body Mass Index (BMI) mediates some of these genetic effects, meaning that weight management can significantly impact your walking ability, even if there’s a genetic predisposition.

5. My doctor says I walk slow; is that a sign of other health issues I should worry about?

Yes, a slower walking pace can be an important early indicator. It’s strongly associated with various health outcomes, including cardiometabolic conditions, and can predict overall health status and even survival. Monitoring changes in your walking ability can therefore help identify potential underlying health problems.

6. Does feeling down or stressed impact my ability to walk effectively?

There’s a genetic connection between walking pace and psychiatric traits, including depressive symptoms and insomnia. This suggests that shared biological pathways might link your mood and mental well-being to your physical ability to walk, highlighting a more holistic relationship than often perceived.

7. Will exercising more really help if slow walking seems to run in my family?

Definitely. While genetics contribute about 13% to walking pace, a substantial portion is influenced by environmental factors, making it highly modifiable. Regular physical activity can help overcome some genetic predispositions, improve muscle strength, and mitigate age-related decline, promoting better mobility regardless of family history.

8. If I’m slower now, does that mean I’ll definitely lose my independence sooner?

A decline in walking ability can indeed increase the risk of reduced physical activity, social isolation, and falls, which can impact your independence and quality of life. Understanding these risks highlights the importance of proactive measures, such as maintaining physical activity, to preserve mobility and strength as you age.

9. Does my ethnic background change my risk for slower walking?

Yes, it can. Most research in this area has focused on individuals of European ancestry. This means the genetic risk factors identified might not be the same or have the same impact in other ethnic groups. More diverse studies are needed to fully understand how ancestry affects walking pace risk across different populations.

10. Is my lung health connected to how fast I can walk?

There’s a significant genetic correlation between walking pace and lung function. This suggests that shared biological mechanisms influence both your respiratory capacity and your ability to walk effectively. Maintaining good lung health can therefore indirectly support your walking ability.

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This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Timmins IR. et al. “Genome-wide association study of self-reported walking pace suggests beneficial effects of brisk walking on health and survival.” Commun Biol. 2020.

[2] Tao F. et al. “Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study.” J Neuromuscul Dis. 2019.

[3] Davies, G., et al. “Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.”Nature Communications, vol. 9, no. 1, 2018, p. 2048.

[4] Tropf, F. C., et al. “Hidden heritability due to heterogeneity across seven populations.” Nature Human Behaviour, vol. 18.

[5] Ludwig KU. et al. “A common variant in myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults.” Transl Psychiatry. 2013.

[6] St Pourcain B. et al. “Common variation near ROBO2 is associated with expressive vocabulary in infancy.” Nat Commun. 2014.