2018/09/22 Detailed phenotyping of sleep and circadian rhythms in a Brazilian community Malcolm von Schantz University of Surrey University of São Paulo www.ifitweremyhome.com Parallels between South Africa and Brazil Leading economies in their continents History of colonisation Have undergone industrialisation and epidemiological transition later and faster than northern hemisphere countries Large differential between extreme wealth and extreme poverty Social and economic segregation largely aligned with racial/ethnic groups Public health care systems with stretched resources Problems with violence and junk food Baependi, Minas Gerais, Brazil (21.95 S 44.88 W) 1
Sunrise, sunset, and daylight hours in Baependi(21.9500 S, 44.8833 W) (https://ptaff.ca/soleil/?lang=en_ca) Self-described ethnicity in the Brazilian 2010 census Estrada Real The Royal Road 400 years of mining, commerce, food production, migration, and racial admixture 2
Analysis of genetic ancestry components in the Baependi cohort shows high degree of admixture (Egan et al, BMJ Open, 2016) Enables analysis of contribution of ancestralities to specific phenotypes European Amerindian African Features of the Baependiheart study cohort (Egan et al, BMJ Open 2016) Population: 18,307 (in 2010 census) High degree of admixture Low inbound migration, mostly from surrounding areas Conservative and traditional lifestyle Less segregated than more developed areas of Brazil Significant level of illiteracy in older individuals High penetrance of electrification Family-based study design (Egan et al, BMJ Open 2016) Proband selected randomly, with subsequent recruitment of extended family pedigrees 95 extended families at baseline Mean pedigree size 24.2 ±31.8 Most families in the study encompass three or four generations Extended family-based design enables analysis of single and joint heritability (= the genetic component of variance) of different traits 3
Collection of cirdadian and sleep-related datasets BaependiHeart Study Cohort, Year 10: 2,239 subjects (>10% of population) 1800 1600 1400 1200 1000 800 600 Active collection Funding secured 400 128 76 200 Egan et al, BMJ Open (2016) 0 MEQ PSQI MCTQ ISI OSA screening Actimetry PSG DLMO Phenotypes collected in the Baependi study Cardiovascular health outcomes Anatomical MRI Genome (Affymetrix) Metabolome (GC-MS, LC-MS) Mental health Home sleep recording Mapping circadian rhythms in Baependi 3D facial imaging Cognition Circadian rhythms (Questionnaires, actimetry, phase markers) Saturday, 22 September 2018 14 4
von Schantz et al, Sci Rep (UK) 2015;5:9214 Distribution of morningness-eveningnessquestionnaire scores in the rural (black) and municipal (grey) zones of Baependi (von Schantz et al, SciRep 2015) Chronotype questionnaires Morningness-eveningness questionnaire (MEQ) (Horne & Östberg, 1976) 19 items Multiple choice questions Questions refer to preferred timings More trait-like useful for heritability studies Combines a circadian and a sleep homeostatic dimension Munich Chronotype Questionnaire (MCTQ) (Roenneberg et al, 2003) 12 items Answers consist of clock times Questions refer to actual timings Allows calculation of mid sleepphase and social jetlag MEQ score as a function of age in the Baependicohort (von Schantz et al, SciRep 2015) 5
Normality plot of MEQ distribution in the Baependicohort (von Schantz et al, SciRep 2015) Average preferred sleep and wake times in Baependi compared to London (Robilliard et al, J Sleep Res 2002) Preferred sleep time Baependi, rural zone Baependi, urban zone London, 7%ile extreme morning types London, intermediate London, 7%ile extreme evening types 21:31 22:29 22:25 23:43 01:32 Preferred wake time 06:46 07:26 07:32 08:47 10:04 Chronotype distribution in São Paulo, London, and Baependi (von Schantz et al, SciRep 2015) 80 70 60 50 40 Covariates Heritability analysis of chronotype(meq score) (von Schantz et al, SciRep 2015) Our data Value Previous publications Publication Value Method Barclay et al, 2010 0.52 MEQ/twins Vink et al, 2001 0.44 0.47 Other/twins 30 20 10 0 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 Baependi London São Paulo None 0.21 Sex, age 0.48 Sex, age, age 2, sex * age 0.48 Sex, age, residence 0.38 Hur et al, 1998 0.45 Other/twins Koskenvuo et al, 2007 0.50 Other/twins Klei et al, 2005 0.23 Other/family Evans et al, 2011 0.21 MEQ family Saturday, 22 September 2018 22 6
MCTQ data: Working days per week (Felipe Beijamini, unpublished) Circadian phase measurement by DLMO (dim light melatonin onset) Half-hourly saliva samples collected at local research station during the evening under dim light conditions Collection performed in spring, near equinox, before switch to daylight savings time Melatonin assays performed by Surrey Assays Ltd and DLMO calculated using 2-SD method Average 20:07±83 min Women 20:30±84 min Men 19:40±73 min) Comparison (Maierova et al, 2016): Extreme morning types 19:33 Extreme evening types 23:26 Social jetlag in the Baependicohort (Felipe Beijamini, unpublished) DLMO and MCTQ data (FrancieliRuiz da Silva & Felipe Beijamini) DLMO 20:07 Sleep onset Weekdays Weekends 23:27 23:44 Sleep offset Weekdays Weekends 06:14 06:57 7
Sample actigraphy (analysis in progress) Mario Pedrazzoli, unpublished Performed in 587 participants (Stardust II, Phillips) Prevalence of obstructive sleep apnoea, (AHI > 5/h): 18.6% (median age 44, median BMI 25.0 kg/m Adjusted heritability calculated to 0.25 Mapping sleep in Baependi 8
Pittsburgh sleep quality index (PSQI) data on timing and quality of sleep (Beijaminiet al, Sci Rep 2016) Average self-reported sleep duration = 07:07±01:31 Average bedtime 22:32±01:27 Average rise time = 06:17±01:25 Average Pittsburgh sleep quality index score = 4.9+3.2 PSQI had very low heritability 0.06 Sleep quality PSQI components (Beijamini et al, Sci Rep 2016) Average sleep time: 07:07 h Self-reportedleepqualityprofile (PSQI) ispoorerthanin moststudiedpopulations(beijaminiet al, SciRep 2016) Insomnia in Baependi (Sabrina S Ahmed, unpublished data) Good sleep quality Poor sleep quality Insomnia severity index (ISI) data collected from 661 participants Consists of questions scored from 0-4 assessing severity of several daytime and night time sleep components, summing up to a score out of 28 Not previously published in population-based setting 9
16% of sample had ISI scores of 15 or above, suggestive of clinical insomnia (Ahmed, unpublished) Local staff were trained to perform home sleep recording (Nihon Kohden TrackIt) Male Female Heritability of ISI, adjusted by age, sex, education, MEQ, and depression, was 0.19 (Ahmed, unpublished) Polysomnography collection to date # collected: 128 # scored: 114 # excluded: 16 Not enough sleep (<4h) 14 failures # Analyzed 98 # with anthropometric & PSG: 95-97 10
PSG Summary Description (Kristen Knutson & Felipe Beijamini) Variable Obs Mean Std. Dev. Min Max Total Recording 98 8.4 1.25 5.7 11.22 Time (h) Total Sleep Time (h) 98 6.3.95 4.25 8.6 Stage 1 (min) 98 37.1 23.7 9 196.5 Stage 2 (min) 98 193.7 40.5 52 290.5 Stage 3 (min) 98 58.7 23.7 0 118.5 REM (min) 98 90.0 34.4 1 170.5 Exclude TST<4h Summary UNIQUE POPULATION The Baependiheart study cohort is a well-established study population in the Brazilian heartland, with a very high level of genetic admixture Conservative and traditional (although not pre-industrial) lifestyle (including diet); high acceptance for participating in the different study protocol UNIQUE DATASETS Opportunity for collecting multiple sleep-related datasets and relating them to a rich tapestry of datasets related to genome, phenomes, physiology, advanced anthropometric measures, and cardiovascular and mental health LONGITUDINAL STUDY The long-term commitment to this study will enable us to investigate how sleep parameters and behavioursdevelop and change in individuals and in the community as a whole Summary of methodologies used Questionnaires Chronotype Morningness-Eveningness Questionnaire (MEQ) Munich Chronotype Questionnaire (MCTQ) Sleep quality and timings Pittsburgh Sleep Quality Index (PSQI) Insomnia Insomnia Severity Index (ISI) Physiological measures OSA screening Actigraphy (exact timings, light exposure, amplitude of activity) Dim Light Melatonin Onset (DLMO) (circadian phase) Polysomnography No population is a living fossil Summary Although no population displays an ancestral diurnal pattern, they may exhibit ancestral aspects The delay caused by electrification may be mitigated by active lifestyle with high light exposure Early sleepers do not necessarily enjoy better sleep 11
Thank you! Academic collaborators Jo Arendt Eve van Cauter Kristen Knutson José Eduardo Krieger Geraldo Lorenzo-Filho Benita Middleton Mario Pedrazzoli Alexandre Pereira Homero Vallada Postdoctoral fellows Andrew Beale Felipe Beijamini Kieren Egan Gal Geovanini André Negrão Francieli Ruiz da Silva PhD students Sabrina Ahmed Tâmara Pessanha Taporoski m.von.schantz@surrey.ac.uk @mvonschantz #SleepHealth2018 12