Genetics, sleep and memory: a recall-by-genotype study of ZNF804A variants and sleep neurophysiology.
BACKGROUND
Schizophrenia is a complex, polygenic disorder for which over 100 genetic variants have been identified that correlate with diagnosis. However, the biological mechanisms underpinning the different symptom clusters remain undefined. The rs1344706 single nucleotide polymorphism within ZNF804A was among the first genetic variants found to be associated with schizophrenia. Previously, neuroimaging and cognitive studies have revealed several associations between rs1344706 and brain structure and function. The aim of this study is to use a recall-by-genotype (RBG) design to investigate the biological basis for the association of ZNF804A variants with schizophrenia. A RBG study, implemented in a population cohort, will be used to evaluate the impact of genetic variation at rs1344706 on sleep neurophysiology and procedural memory consolidation in healthy participants.


METHODS
Participants will be recruited from the Avon Longitudinal Study of Parents and Children (ALSPAC) on the basis of genotype at rs1344706 (n = 24). Each participant will be asked to take part in two nights of in-depth sleep monitoring (polysomnography) allowing collection of neurophysiological sleep data in a manner not amenable to large-scale study. Sleep questionnaires will be used to assess general sleep quality and subjective sleep experience after each in-house recording. A motor sequencing task (MST) will be performed before and after the second night of polysomnography. In order to gather additional data about habitual sleep behaviour participants will be asked to wear a wrist worn activity monitor (actiwatch) and complete a sleep diary for two weeks.


CONCLUSIONS
This study will explore the biological function of ZNF804A genotype (rs1344706) in healthy volunteers by examining detailed features of sleep architecture and physiology in relation to motor learning. Using a RBG approach will enable us to collect precise and detailed phenotypic data whilst achieving an informative biological gradient. It would not be feasible to collect such data in the large sample sizes that would be required under a random sampling scheme. By dissecting the role of individual variants associated with schizophrenia in this way, we can begin to unravel the complex genetic mechanisms of psychiatric disorders and pave the way for future development of novel therapeutic approaches.
School of Physiology and Pharmacology, University of Bristol, Bristol, UK. charlotte.hellmich@googlemail.com.
Charlotte
C
Hellmich
Clinical Research and Imaging Centre (CRICBristol), University of Bristol, Bristol, UK. Claire.Durant@bristol.ac.uk.
Claire
C
Durant
School of Physiology and Pharmacology, University of Bristol, Bristol, UK. Matt.Jones@bristol.ac.uk.
Matthew W
MW
Jones
MRC Integrative Epidemiology Unit at University of Bristol, Bristol, UK. N.J.Timpson@bristol.ac.uk.
Nicholas J
NJ
Timpson
School of Physiology and Pharmacology, University of Bristol, Bristol, UK. Ullrich.Bartsch@bristol.ac.uk.
Ullrich
U
Bartsch
MRC Integrative Epidemiology Unit at University of Bristol, Bristol, UK. laura.corbin@bristol.ac.uk.
Laura J
LJ
Corbin
D000328:Adult; D001921:Brain / Q000502:physiology; D064368:Healthy Volunteers / Q000523:psychology; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D000069077:Memory Consolidation / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D017286:Polysomnography / Q000379:methods; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology; D012890:Sleep / Q000502:physiology*; D011795:Surveys and Questionnaires; D055815:Young Adult
D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human