Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

This article is part of the PlexusDx Education Hub — your resource for evidence-based guidance on diet & genetics. Browse all Diet & Genetics education

Some people are restless and drawn to movement; others have to fight hard to leave the couch. That difference is not just willpower. Twin and population studies show that the drive to be physically active — and the tendency toward sedentary behavior — is meaningfully heritable. Your genes influence the reward you feel from exercise, how your muscles respond to it, and how your body handles energy. Knowing that biology reframes the fight against a sedentary lifestyle.

How much of activity level is genetic?

More than most people assume. Twin studies estimate that 40 to 60 percent of the variation in habitual physical activity is heritable, and large genome-wide studies have identified specific locations in the genome linked to how much people move and how much they sit. The remaining variation is environmental — access, schedule, injury, motivation, and habit. Genetics sets a predisposition, not a life sentence, and behavior can shift the outcome substantially.

The dopamine reward pathway: DRD2 and motivation to move

A large part of exercise "wanting" runs through dopamine, the brain's reward and motivation signal. The dopamine D2 receptor gene, DRD2, and related dopamine-signaling genes influence how rewarding physical activity feels. Research in both animals and humans links variation in this pathway to voluntary exercise behavior: individuals whose reward circuitry responds strongly to movement tend to seek it out, while those with blunted signaling find it easier to stay still. This helps explain why "just push through it" works for some and not others.

CADM2 and the biology of movement propensity

Among the most consistently replicated genes for physical activity is CADM2, which is active in the brain and involved in neuronal connectivity and energy balance. Large genome-wide association studies tie CADM2 variants to differences in both self-reported and device-measured physical activity, as well as to sedentary time and related metabolic traits. It sits at the intersection of behavior and metabolism, which is exactly where the propensity to move is decided.

Metabolism and exercise response: FTO and PPARGC1A

Genes also shape what happens when you do move. The FTO gene, best known for its association with body weight and appetite, also interacts with physical activity — and notably, staying active appears to blunt the weight effect of high-risk FTO variants, a clear example of genes and behavior working together. Meanwhile PPARGC1A, which encodes the metabolic regulator PGC-1-alpha, influences how muscle builds mitochondria and adapts to training. Two people can follow the same routine and adapt at different rates because of pathways like these.

Combating sedentary behavior with your biology in mind

Pathway-level genetic insight will not write your workout plan, but it can change your strategy. The Precision Peptide Genetic Test analyzes 14 pathways, 49 peptides, 150+ genetic insights, including variants across dopamine-reward and energy-metabolism pathways. If your reward signaling for exercise runs low, the practical takeaway is structural: build movement into non-negotiable routines, pair it with social or reward cues, and pick activities your biology actually enjoys rather than relying on motivation alone. PlexusDx tells you about your biology; it does not tell you what to put in your body. A qualified provider or coach helps translate that context into a plan.

Frequently Asked Questions

What percent of physical activity is genetic?

Twin studies estimate roughly 40 to 60 percent of the variation in habitual physical activity is heritable. The rest reflects environment, access, injury, and habit. Genetics shapes your baseline drive to move, but behavior and circumstances substantially determine how active you actually become.

Which genes affect the motivation to exercise?

Dopamine-signaling genes such as DRD2 influence how rewarding movement feels, while CADM2 is repeatedly linked to physical-activity and sedentary-time differences. These genes shape the propensity to move, not a guarantee. Environment and routine still play a major role in actual activity levels.

Can I overcome a genetic tendency toward sedentary behavior?

Yes. Heritability sets a predisposition, not a ceiling. Research on FTO shows that staying active blunts genetic weight risk, a clear sign that behavior overrides biology in part. Structured routines, reward cues, and enjoyable activities help work with, rather than against, your genetics.

Does genetic testing tell me the best workout for me?

No. A genetic test reports pathway-level tendencies in reward and energy metabolism — it does not prescribe a workout or predict performance. Use the context to shape strategy with a qualified provider or coach, who tailors any exercise plan to your goals and health.

Curious how your own biology maps to these pathways? The Precision Peptide Genetic Test reads 14 pathways, 49 peptides, 150+ genetic insights across a single at-home saliva sample, giving you pathway-level context to bring to a qualified provider. Know your genetics; don't guess.

This article is part of the PlexusDx Education Hub. Browse all Diet & Genetics education

The Precision Peptide Genetic Test analyzes how your genes influence peptide-related biological pathways. It does not recommend, prescribe, or determine which peptides you should use. Consult a qualified healthcare provider before beginning any peptide protocol.

Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.