Genetics and Seasonal Affective Disorder

Key takeaways:
~ Seasonal Affective Disorder (SAD) affects 5-10% of the population in higher latitudes.
~ Genetic variants in circadian rhythm and light detection genes are linked to increased susceptibility to SAD.
~ Changing your lighting may help you beat the winter blues.

This article dives into the science of why seasonal affective disorder occurs, which genetic variants increase susceptibility, and the personalized solutions that may work for specific genetic variants. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

What is Seasonal Affective Disorder?

The Winter Blues… It’s often described as feeling low, generally apathetic, blah, usually accompanied by changes in sleep.

Officially called Seasonal Affective Disorder, the change in mood when the days grow short is a fairly common phenomenon in higher latitudes. It affects 5-10% of some populations.[ref]

Seasonal Affective Disorder (SAD) is characterized by recurrent depression with a change in the season, usually in fall/winter for most people.

Scientists think SAD is due to an aberrant or altered response to light. It could be due to not enough brightness from sunlight or simply not enough hours of light.

SAD is considered to be highly heritable, and studies in twins show that about 50% of the risk is genetic.[ref] What is the other half of the equation here? Daylight exposure is a big one. Chronic inflammation may also increase the risk.

Researchers can determine what causes a problem – the root cause – by finding out which genes enhance the likelihood of a disease or disorder.

Knowing the genes involved can help us understand which biological pathways are involved.

For seasonal affective disorder, research pinpoints many genes that encode circadian rhythm proteins.[ref]

Circadian rhythm and SAD:

Our circadian rhythm is controlled by genes triggered by light hitting the retina of our eyes.

During the daytime, light in the blue spectrum hits specific receptors in the retina and shuts off melatonin production from the pineal gland. This process occurs when blue light hits a specific receptor (OPN4), triggering a signal to the brain to stop melatonin from being produced.[ref]

At night, the lack of light in the blue wavelengths allows melatonin levels to rise again.

Both the suppression of melatonin during daylight via exposure to bright light and the rise of melatonin at night due to darkness are integral to mental and physical health.

The lack of light during the daytime may affect seasonal depression by not shutting off melatonin production enough during the day.[ref]

Interestingly, some genes associated with SAD also overlap with genetic variants that increase susceptibility to bipolar disorder and schizophrenia but not other depressive disorders.[ref] For many, bipolar disorder is linked to circadian rhythm disruption.

Related article: Circadian rhythm genes and bipolar disorder

The core circadian clock genes include a pair of genes (CLOCK and BMAL1) active together during the daytime and another pair of genes (PER and CRY) active during the nighttime.

The rise and fall of these genes create a 24-hour molecular clock that governs many cellular functions throughout the body.

Messing up your circadian rhythm makes you feel bad…

If you have ever traveled across several time zones, you know that jetlag can make you feel a bit wretched for a day or two. For me, jetlag makes me feel disoriented, grumpy, and unable to think clearly.

The feelings of jetlag are due to your circadian clock being out of sync with your environment. Your body thinks it is midnight, but your eyes know that the sun is up and shining brightly.

When your circadian rhythm is disrupted — whether from travel or staying up late, or changing light — the result can cause physiological changes in how your body feels and your mind works.

Serotonin and SAD:

You may be wondering, but what about serotonin? Everyone thinks of serotonin for depression due to the popularity of SSRIs as antidepressant drugs.

Several studies for seasonal affective disorder have looked into the link to serotonin. While most of the studies didn’t find a significant link to serotonin genes, the way serotonin is used in the brain may play a role in SAD.[ref][ref][ref] For example, certain behaviors linked with seasonal depression, such as overeating, may be related to serotonin.[ref]

Interestingly, a couple of studies have found that a serotonin receptor, HTR2A, is significantly associated with seasonal depression in both winter and summer. This receptor involves memory, mood, cognition, appetite, anxiety, perception, sleep, thermoregulation, and vasoconstriction. It is activated by serotonin, LSD, psilocybin, and DMT.

Related article: Serotonin receptor 2A genetic variants

Is there a SAD gene?

While genes do play a major role in increasing the risk of SAD, there is not one specific gene mutation that causes seasonal affective disorder.

Instead, multiple genetic variants add to the risk, along with latitude, length of daylight, and possibly dietary factors.

Additionally, seasonal changes occur in most mammals to neurotransmitter levels.

Monoamine Oxidase (MAO-A) Levels change seasonally

MAO-A is an enzyme that breaks down neurotransmitters, and changes in MAO-A levels are linked to depressive disorders.

Recently, researchers discovered that most people normally have a seasonal change in MAO-A levels in the fall and winter. But people with SAD don’t have that normal, seasonal rhythm to MAO-A levels. Important here, the researchers also found that bright light therapy restored the normal MAO-A seasonal dynamics.[ref]

Seasonal Affective Disorder Genotype Report

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PER3 Gene:

The PER3 gene has been tied to the seasonal effect of shorter daylight hours in many studies. All of the PER (Period) genes (PER1, PER2, and PER3) play a central role in our body’s circadian rhythm. PER1 and PER2 genetic variants can cause disruptions in sleep and a shift in circadian rhythm. PER3 genetic variants have been linked specifically to mood changes due to shorter daylight hours in the winter. The slight shift in circadian rhythm from the PER3 genetic variant coupled with the change in daylight may be what causes SAD for some people.[ref][ref][ref][ref][ref]

Check your genetic data for rs139315125 (23andMe v5):

  • A/A: typical
  • A/G: less PER3, higher risk of SAD
  • G/G: decreased PER3, higher risk of SAD, delayed sleep phase disorder[ref]

Members: Your genotype for rs139315125 is .

Check your genetic data for rs150812083 (23andMe v5):

  • C/C: typical
  • C/G: less PER3, higher risk of SAD
  • G/G: decreased PER3, higher risk of SAD, advanced sleep phase disorder[ref][ref]

Members: Your genotype for rs150812083 is .

Check your genetic data for rs228697 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/G: linked to evening preference; higher risk of anxiety disorders, SAD
  • G/G: linked to evening preference; higher risk of anxiety disorders, SAD[ref][ref][ref]

Members: Your genotype for rs228697 is .

OPN4 – melanopsin gene:

Melanopsin is the non-visual photopigment in your retina that sets the circadian clock. It is thought that lower levels of melanopsin may contribute to the risk of SAD because of the lower light levels in the winter. Melanopsin is involved in photo-entrainment, negative masking, and pupillary light reflex. Essentially, it is excited by light in the blue wavelengths (~480nm) and relays a signal to the brain that it is daytime.

Check your genetic data for rs2675703 P10L (23andMe v5; AncestryDNA):

  • C/C: typical
  • C/T: increased risk of SAD
  • T/T: 5.6x more likely to have SAD; heightened responsivity to day length.[ref][ref]

Members: Your genotype for rs2675703 is .

Check your genetic data for rs1079610 I394T (AncestryDNA):

  • T/T: typical
  • C/T: response to light, earlier sleep/wake timing
  • C/C: increased response to blue light[ref]; earlier sleep/wake timing[ref], linked with SAD (small study)[ref]

Members: Your genotype for rs1079610 is .


The Circadian Locomotion Output Kaput (CLOCK) gene is one of the core genes that set our daily rhythms.

Check your genetic data for rs1801260 (23andMe v4, v5: AncestryDNA)

  • A/A: typical
  • A/G: typical risk of SAD, increased evening activity
  • G/G: decreased risk of SAD; a higher level of activity in the evening.[ref][ref]

Members: Your genotype for rs1801260 is .

HTR2A gene: encodes the serotonin 2A receptor. It is the same receptor activated by psychedelics

Check your genetic data for rs731779 (23andMe v4; AncestryDNA):

  • C/C: increased risk of SAD
  • A/C: typical risk
  • A/A: typical

Members: Your genotype for rs731779 is .

Lifehacks for Seasonal Affective Disorder

First and foremost: going outside first thing in the morning may help if you live at a middle latitude. The morning sun is powerful in resetting your circadian rhythm.

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Related Articles and Topics:

Serotonin: Genetic variants that impact serotonin levels and serotonin receptors
Serotonin is a neurotransmitter that is important in depression, sleep, and many other aspects of health. Learn how your genetic variants in the serotonin receptor genes impact their function.

COMT Gene: Neurotransmitters, estrogen metabolism, and more
Wondering why your neurotransmitters are out of balance? It could be due to your COMT genetic variants. The COMT gene codes for the enzyme catechol-O-methyltransferase, which breaks down (metabolizes) the neurotransmitters dopamine, epinephrine, and norepinephrine.



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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.

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