Melatonin receptor gene: Alzheimer’s risk and night shift work

Shift work and ‘social jet lag’ are linked to an increased risk for several chronic diseases. Shift work is usually defined in studies as working a late or early shift more than two times per week, while social jet lag is the term for staying up late and then sleeping in on the weekends in contrast to a sleep schedule that is hours earlier during the work-week.

How does shift work affect health?

Let me throw a few quick studies at you about the impact of shift work / social jet lag:

  • Solid research links shift work to an increased risk of cancer, specifically breast and prostate cancer[ref][ref][ref]
  • Shift work increases the risk of being overweight[ref][ref][ref]
  • It also increases the risk that your children will be overweight[ref]
  • Shift workers are at an increased risk for diabetes[ref][ref]
  • It also increases the risk of Alzheimer’s and dementia[ref]

You may be thinking…I work the night shift and am just fine with it!

Like most things, it turns out that genetics plays a role in how much shift work impacts you.

Variants in the melatonin receptor gene:

While some people may get along well with shift work, others may experience more difficulties with it. A new study found one genetic variant that may shed some light on the topic (pun intended :-).

Scientists recently found that a melatonin receptor variant (MTNR1A gene) was associated with an increased likelihood of fatigue and other ill effects when working the night shift. The study looked at several different groups of night shift workers including flight attendants, pilots, and nurses. It found that those who carried the MTNR1A variant and worked the night shift more than were more likely to have higher fatigue scores. A control group that didn’t work the night shift had no effect from the MTNR1A variant. The researchers believe this variant causes fewer melatonin receptors in the brain.[ref]

Is Alzheimer’s disease linked to melatonin?

This same variant is also linked to an increased risk of Alzheimer’s disease. In a cohort of those aged 85 and older, it was found that those with the rs12506228 A-allele were at about double the risk of Alzheimer’s.[ref]

Related Article: Alzheimer’s and APOE genotype


MTNR1A Genotype Report:

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Check your genetic data for rs12506228 (23andMe v4, v5; AncestryDNA):

  • A/A: likely fewer melatonin receptors in the brain, a greater impact from working the night shift, increased risk of Alzheimer’s.[ref][ref]
  • A/C: somewhat fewer melatonin receptors, somewhat impacted from light at night, increased risk of Alzheimer’s
  • C/C: typical MTNR1A variant

Members: Your genotype for rs12506228 is .

The researchers think that the reason that the variant increases the risk for Alzheimer’s and fatigue from shift work is due to a decrease in the number of melatonin receptors in the brain. Specifically, a decreased number of melatonin receptors in the suprachiasmatic nucleus may be causing increased sensitivity to light at night.[ref]


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References:

Hansen, Anne B., et al. “Night Shift Work and Incidence of Diabetes in the Danish Nurse Cohort.” Occupational and Environmental Medicine, vol. 73, no. 4, Apr. 2016, pp. 262–68. PubMed, https://doi.org/10.1136/oemed-2015-103342.
Hansen, Johnni, and Christina F. Lassen. “Nested Case-Control Study of Night Shift Work and Breast Cancer Risk among Women in the Danish Military.” Occupational and Environmental Medicine, vol. 69, no. 8, Aug. 2012, pp. 551–56. PubMed, https://doi.org/10.1136/oemed-2011-100240.
Jørgensen, Jeanette Therming, et al. “Shift Work and Overall and Cause-Specific Mortality in the Danish Nurse Cohort.” Scandinavian Journal of Work, Environment & Health, vol. 43, no. 2, Mar. 2017, pp. 117–26. PubMed, https://doi.org/10.5271/sjweh.3612.
Kim, Min-Ju, et al. “Association between Shift Work and Obesity among Female Nurses: Korean Nurses’ Survey.” BMC Public Health, vol. 13, Dec. 2013, p. 1204. PubMed, https://doi.org/10.1186/1471-2458-13-1204.
McGlynn, Natalie, et al. “Shift Work and Obesity among Canadian Women: A Cross-Sectional Study Using a Novel Exposure Assessment Tool.” PloS One, vol. 10, no. 9, 2015, p. e0137561. PubMed, https://doi.org/10.1371/journal.pone.0137561.
Pan, An, et al. “Rotating Night Shift Work and Risk of Type 2 Diabetes: Two Prospective Cohort Studies in Women.” PLoS Medicine, vol. 8, no. 12, Dec. 2011, p. e1001141. PubMed, https://doi.org/10.1371/journal.pmed.1001141.
Papantoniou, Kyriaki, et al. “Night Shift Work, Chronotype and Prostate Cancer Risk in the MCC-Spain Case-Control Study.” International Journal of Cancer, vol. 137, no. 5, Sept. 2015, pp. 1147–57. PubMed, https://doi.org/10.1002/ijc.29400.
Strohmaier, Susanne, et al. “Night Shift Work Before and During Pregnancy and Offspring Weight Outcomes Through Adolescence.” Obesity (Silver Spring, Md.), vol. 26, no. 9, Sept. 2018, pp. 1491–500. PubMed, https://doi.org/10.1002/oby.22267.
Sulkava, Sonja, Hanna M. Ollila, et al. “Common Genetic Variation Near Melatonin Receptor 1A Gene Linked to Job-Related Exhaustion in Shift Workers.” Sleep, vol. 40, no. 1, Feb. 2017, p. zsw011. PubMed Central, https://doi.org/10.1093/sleep/zsw011.
—. “Common Genetic Variation Near Melatonin Receptor 1A Gene Linked to Job-Related Exhaustion in Shift Workers.” Sleep, vol. 40, no. 1, Feb. 2017, p. zsw011. PubMed Central, https://doi.org/10.1093/sleep/zsw011.
Sulkava, Sonja, Pranuthi Muggalla, et al. “Melatonin Receptor Type 1A Gene Linked to Alzheimer’s Disease in Old Age.” Sleep, vol. 41, no. 7, July 2018, p. zsy103. PubMed Central, https://doi.org/10.1093/sleep/zsy103.
—. “Melatonin Receptor Type 1A Gene Linked to Alzheimer’s Disease in Old Age.” Sleep, vol. 41, no. 7, July 2018, p. zsy103. PubMed Central, https://doi.org/10.1093/sleep/zsy103.
Sun, Miaomiao, et al. “Night Shift Work Exposure Profile and Obesity: Baseline Results from a Chinese Night Shift Worker Cohort.” PloS One, vol. 13, no. 5, 2018, p. e0196989. PubMed, https://doi.org/10.1371/journal.pone.0196989.
Wang, Pan, et al. “Night-Shift Work, Sleep Duration, Daytime Napping, and Breast Cancer Risk.” Sleep Medicine, vol. 16, no. 4, Apr. 2015, pp. 462–68. PubMed, https://doi.org/10.1016/j.sleep.2014.11.017.


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.