Important environmental cue
reviewed
|
Temperature, changes with season and latitude |
Direction of
effect
|
Cold temperature stimulates expression of peptide agonist; MCHR1 controls thermo-regulation to lower body temperature and conserve BAT |
Risk of schizophrenia (scz)
consistent with known gene
function?
|
Yes:
-
(1)
season-of-birth effect
-
(2)
scz more common in populations in higher latitudes
-
(3)
ICV administration of peptide agonist in rats elicits auditory gating pattern consistent with scz
-
(4)
lower body temperature and over-dressing in scz
-
(5)
MCHR1 controls REM sleep, disrupted in scz
-
(6)
brain-region specific expression consistent with major pathways dysreg. in scz
-
(7)
co-localizes with tyrosine hydroxylase in the brain, a marker of dopamine synthesis
|
Strength
of genetic
association
|
Moderate: 4 positive studies; and 1 positive when part of a complex genotype; contributes to PRS; the alleles conferring risk depend on the population |
Epigenetic data
of relevance?
|
Yes:
-
(1)
4 alleles linked in genetic association studies are located in (+/−) CpG sites
-
(2)
1st exon CpG site is hypomethylated in psychosis (two studies)
-
(3)
evidence that methylation may control alternative splicing
-
(4)
smoking hypermethylates a CpG site in the 5′UTR region; predicted to affect expression of the 353aa MCHR1 protein reported by NCBI; hypermethylation in the promoter region may decrease expression of the 353aa protein and/or the alternative 422aa protein (the latter via alternative splicing).
-
(5)
the methylation difference between the rs133072 and rs13373 haplotypes is greatest in the age range of greatest risk for scz, 20 to 30 years of age
|
|
Consistency of gene expression data
|
One study: gene expression decreased in scz, but may be confounded by smoking based on methylation pattern identified in smokers |
