Genetic adaptation of the human circadian clock to day-length latitudinal variations and relevance for affective disorders

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17 Citations (Scopus)

Abstract

Background: The temporal coordination of biological processes into daily cycles is a common feature of most living organisms. In humans, disruption of circadian rhythms is commonly observed in psychiatric diseases, including schizophrenia, bipolar disorder, depression and autism. Light therapy is the most effective treatment for seasonal affective disorder and circadian-related treatments sustain antidepressant response in bipolar disorder patients. Day/night cycles represent a major circadian synchronizing signal and vary widely with latitude. Results: We apply a geographically explicit model to show that out-of-Africa migration, which led humans to occupy a wide latitudinal area, affected the evolutionary history of circadian regulatory genes. The SNPs we identify using this model display consistent signals of natural selection using tests based on population genetic differentiation and haplotype homozygosity. Signals of natural selection driven by annual photoperiod variation are detected for schizophrenia, bipolar disorder, and restless leg syndrome risk variants, in line with the circadian component of these conditions. Conclusions: Our results suggest that human populations adapted to life at different latitudes by tuning their circadian clock systems. This process also involves risk variants for neuropsychiatric conditions, suggesting possible genetic modulators for chronotherapies and candidates for interaction analysis with photoperiod-related environmental variables, such as season of birth, country of residence, shift-work or lifestyle habits.

Original languageEnglish
Article number499
JournalGenome Biology
Volume15
Issue number10
DOIs
Publication statusPublished - Oct 30 2014

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day length
Circadian Clocks
Medical Genetics
Mood Disorders
Bipolar Disorder
circadian rhythm
natural selection
photoperiod
antidepressants
work schedules
Genetic Selection
Photoperiod
homozygosity
regulator genes
human population
lifestyle
population genetics
Schizophrenia
haplotypes
legs

ASJC Scopus subject areas

  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics
  • Genetics

Cite this

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title = "Genetic adaptation of the human circadian clock to day-length latitudinal variations and relevance for affective disorders",
abstract = "Background: The temporal coordination of biological processes into daily cycles is a common feature of most living organisms. In humans, disruption of circadian rhythms is commonly observed in psychiatric diseases, including schizophrenia, bipolar disorder, depression and autism. Light therapy is the most effective treatment for seasonal affective disorder and circadian-related treatments sustain antidepressant response in bipolar disorder patients. Day/night cycles represent a major circadian synchronizing signal and vary widely with latitude. Results: We apply a geographically explicit model to show that out-of-Africa migration, which led humans to occupy a wide latitudinal area, affected the evolutionary history of circadian regulatory genes. The SNPs we identify using this model display consistent signals of natural selection using tests based on population genetic differentiation and haplotype homozygosity. Signals of natural selection driven by annual photoperiod variation are detected for schizophrenia, bipolar disorder, and restless leg syndrome risk variants, in line with the circadian component of these conditions. Conclusions: Our results suggest that human populations adapted to life at different latitudes by tuning their circadian clock systems. This process also involves risk variants for neuropsychiatric conditions, suggesting possible genetic modulators for chronotherapies and candidates for interaction analysis with photoperiod-related environmental variables, such as season of birth, country of residence, shift-work or lifestyle habits.",
author = "Diego Forni and Uberto Pozzoli and Rachele Cagliani and Claudia Tresoldi and Giorgia Menozzi and Stefania Riva and Guerini, {Franca R.} and Comi, {Giacomo P.} and Elisabetta Bolognesi and Nereo Bresolin and Mario Clerici and Manuela Sironi",
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T1 - Genetic adaptation of the human circadian clock to day-length latitudinal variations and relevance for affective disorders

AU - Forni, Diego

AU - Pozzoli, Uberto

AU - Cagliani, Rachele

AU - Tresoldi, Claudia

AU - Menozzi, Giorgia

AU - Riva, Stefania

AU - Guerini, Franca R.

AU - Comi, Giacomo P.

AU - Bolognesi, Elisabetta

AU - Bresolin, Nereo

AU - Clerici, Mario

AU - Sironi, Manuela

PY - 2014/10/30

Y1 - 2014/10/30

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