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Doenças cardiovasculares (DCVs) são a principal causa de morbidade e mortalidade no mundo e a etnia do indivíduo tem uma importante influência no diagnóstico e tratamento dessas doenças. No entanto, as bases das disparidades étnicas ainda não estão completamente esclarecidas. O estudo de uma população com alta miscigenação genética, fornece potenciais maneiras de compreender a influência genética na determinação de fenótipos de doenças complexas, como as cardiovasculares, em raízes ancestrais comuns. O presente estudo teve como objetivo principal associar etnia auto referida e ancestralidade genética em indivíduos de uma coorte brasileira com fatores de risco para doenças cardiovasculares. Identificamos associação entre etnia auto referida e hipertensão arterial, acidente vascular cerebral (AVC) e hipercolesterolemia. Analisando a hipercolesterolemia com mais detalhes, encontramos associação de etnia com níveis séricos de triglicerídeos (TG), lipoproteína de alta densidade (HDL-c) e índice TG/HDL-c. Essas associações foram fortemente dependentes de confundidores socioeconômicos, mas variações existem na força e direção de cada padrão. No entanto, observamos que o efeito de etnia persistiu mesmo após todas as correções. Em seguida derivamos um painel de marcadores para inferir ancestralidade genética continental, para os componentes ancestrais africano, europeu e ameríndio, e determinamos as proporções de ancestralidade na nossa população de estudo. Na sequência, conduzimos análises de associação entre ancestralidade genética e níveis séricos de lipídios, a fim de estudarmos uma variável menos influenciada por fatores socioeconômicos. Nessas análises encontramos associação entre a ancestralidade ameríndia e níveis séricos de HDL-c. Entender porque essa heterogeneidade existe pode prover importantes pistas sobre as razões para uma importante parte das disparidades étnicas em doenças cardiovasculares / Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in the world and ethnicity plays an important influence on diagnosis and treatment of these diseases. However, the basis of these ethnic disparities are not fully understood. Studying a population with a high genetic admixture allows potential ways to understand the genetic influence on determination of complex disease phenotypes, such as cardiovascular, in common ancestral roots. The present study had as main aim associating self-reported ethnicity and genetic ancestry in individuals from a Brazilian cohort which have risk factors for cardiovascular diseases. We identified association between self-reported ethnicity and arterial hypertension, stroke, and hypercholesterolemia. Analyzing hypercholesterolemia more deeply, we found association of ethnicity with serum levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-c), and TG/HDL-c index. These associations were strongly dependent on socioeconomic confounders, but there are variations in the strength and direction of each pattern. However, we observed that the ethnicity effect persisted even after all adjustments. Following, we derived a panel of markers to infer continental genetic ancestry for African, European and Amerindian ancestral components, and we have determined the ancestral proportions of ancestry in our study population. After that, we conducted association analysis between genetic ancestry and lipids serum levels, in order to study a variable which is less influenced by socioeconomic factors. In these analyzes we found association between Amerindian ancestry and serum levels of HDL-c. Understanding why there is this heterogeneity can provide important clues about the reason for an important part of ethnic disparities in cardiovascular diseases

Yuen, Wing Ki. / "June 2008." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 44-58). / Abstracts in English and Chinese, some text in appendix also in Chinese. / Acknowledgements --- p.2 / Abstract --- p.3 / Table of Contents --- p.5 / List of Tables --- p.8 / List of Figures --- p.9 / CHAPTER / Chapter 1. --- INTRODUCTION --- p.11 / Purpose of the Study --- p.12 / Hypotheses --- p.12 / Chapter 2. --- LITERATURE REVIEW --- p.13 / Chapter 3. --- METHODS --- p.17 / Study population --- p.17 / Aerobic Capacity of Apparently Healthy Hong Kong Population --- p.17 / Mr Os and Ms Os --- p.18 / Recruitment of subjects --- p.19 / Chapter (a) --- Relationship between age and vBMD for the Chinese population using pQCT --- p.19 / Chapter (b) --- Risk factors for vBMD in peripheral sites --- p.20 / Chapter (c) --- Performance of pQCT and DXA on fracture discrimination --- p.20 / Subject inclusion and exclusion criteria --- p.21 / Interview and questionnaire --- p.21 / Anthropometric measurements --- p.22 / Overall health and medication --- p.22 / Cigarette smoking and alcohol consumption --- p.23 / Grip strength --- p.23 / Physical activity --- p.23 / Walking speed --- p.23 / Assessment of fracture case --- p.24 / Incident fracture --- p.24 / Bone Mineral Measurements --- p.24 / pQCT measurement --- p.24 / DXA measurement --- p.25 / Statistical Analysis --- p.26 / Chapter 4. --- RESULTS --- p.27 / Chapter (a) --- Relationship between age and vBMD for the Chinese population using pQCT --- p.27 / Chapter (b) --- Risk factors for vBMD in peripheral sites --- p.29 / Lifestyle factors --- p.29 / Medical history and medications --- p.30 / Fracture history --- p.30 / Multivariate model --- p.30 / Chapter (c) --- Performance of pQCT and DXA on fracture discrimination --- p.31 / Chapter 5. --- DISCUSSION --- p.33 / Relationship between age and vBMD for the Chinese population using pQCT --- p.33 / Risk factors for vBMD in peripheral sites --- p.36 / Performance of pQCT and DXA on fracture discrimination --- p.39 / Limitations --- p.42 / Conclusion --- p.42 / Reference --- p.44 / Appendix --- p.84 / Chapter A) --- Informed Consent Form --- p.84 / Chapter B) --- Medical Record Consent Form --- p.86 / Chapter C) --- MrOs/ MsOs baseline Questionnaire --- p.87 / Chapter D) --- MrOs/ MsOs Physical Measurement Questionnaire --- p.111 / Chapter E) --- MrOs/ MsOs follow-up Questionnaire --- p.120

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-08-30T21:44:55Z No. of bitstreams: 1 Thais Ferreira Bonfim. Ancestralidade genômica em uma amostra de portadores do HIV-1 do Estado da Bahia - CPqGM - Dissertação de Mestrado - 2008.pdf: 2375743 bytes, checksum: 3d0b1edd686e7965b81d1f26113f0f78 (MD5) / Made available in DSpace on 2012-08-30T21:44:55Z (GMT). No. of bitstreams: 1 Thais Ferreira Bonfim. Ancestralidade genômica em uma amostra de portadores do HIV-1 do Estado da Bahia - CPqGM - Dissertação de Mestrado - 2008.pdf: 2375743 bytes, checksum: 3d0b1edd686e7965b81d1f26113f0f78 (MD5) Previous issue date: 2012 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / A população brasileira apresenta extensa variabilidade genética, resultado da miscigenação entre ameríndios, europeus e africanos. Contudo, a proporção de africanos, ameríndios e europeus difere significativamente a depender da região geográfica. Atualmente são utilizados marcadores moleculares conhecidos como Marcadores Informativos de Ancestralidade (AIM) para avaliar mistura genética nas populações. A cor da pele é um dos fenótipos que mais variam entre e em populações humanas de diferentes etnias e regiões geográficas, devido à grande heterogeneidade gênica e ação da seleção natural. Muitos genes já foram descritos como associados à pigmentação, e alguns deles apresentam frequências alélicas distintas entre diferentes grupos étnicos, porém os mecanismos que respondem pela variação da pigmentação normal da pele ainda não estão completamente estabelecidos. O objetivo deste estudo foi estimar a ancestralidade genética, analisar polimorfismos em genes que modulam a variação normal da pigmentação da pele e verificar associação entre ancestralidade e pigmentação, utilizando nove AIM (AT3-I/D, APO, SB19.3, PV92, FYnull, LPL, CKMM, GC-F, GC-S e CYP3A4), seis polimorfismos em genes envolvidos na pigmentação da pele (SCL45A2, SCL24A5, MC1R, OCA2, TYR, ASIP) em duas tribos indígenas do Norte do Brasil – Tiriyó e Waiampi; em indivíduos caracterizados fenotipicamente como negros de Salvador, numa amostra de miscigenados da Bahia e em descendentes de japoneses e de europeus de Ribeirão Preto-SP. As frequências alélicas de todos os marcadores encontradas nos afro e eurodescendentes foram similares às encontradas nos ancestrais africanos e europeus e a estimativa de mistura mostrou respectivamente maior contribuição africana - 71% e 66%; e europeia - 86% e 99% com AIM e com os marcadores de pigmentação respectivamente. Os japoneses mostraram frequências alélicas diferentes quando comparadas com os Nativos Americanos, e a contribuição Ameríndia/Asiática observada foi 81% com AIM e 86% com marcadores de pigmentação. Entre os índios Tiriyó e Waiampi foi observada baixa contribuição de povos não indígenas nas estimativas de mistura com AIM (< 10%) e nenhuma mistura quando avaliados apenas os marcadores de pigmentação, sugerindo que essas tribos conservam muitas características ancestrais. As estimativas de mistura nos indivíduos miscigenados da Bahia mostrou predomínio de contribuição europeia utilizando os marcadores de pigmentação da pele e maior contribuição africana utilizando os AIM. A distribuição genotípica dos marcadores de pigmentação da pele foi concordante com a classificação fenotípica realizada nos miscigenados (Bahia) em brancos, mulatos e negros, corroborando dados da literatura que mostram o envolvimento desses marcadores na variação normal da pigmentação da pele em diferentes grupos étnicos. / The Brazilian population presents extensive genetic variability, resulting from admixture among Amerindian, Europeans and Africans. However, the proportion of Africans Amerindians and Europeans differ depending on the geographic region. To evaluate the admixture and understand how it occurred, nowadays has been used molecular markers known as Ancestry Informative Markers (AIMs). Skin color is one of the phenotypes that vary most among human populations and different ethnic groups and geographic regions, due to genetic heterogeneity and natural selection. Many genes that are involved in the synthesis of melanin, and proteins involved in cellular metabolism have been described as associated with pigmentation (eye color, hair and skin), and some of them have different allele frequencies between different ethnic groups, but the mechanisms that involved with the variation of the normal skin pigmentation are not yet fully established. The aims of this study was to estimate the genomic ancestry and analyze polymorphisms in genes that modulate normal variation in pigmentation and verify the association between ancestry and skin pigmentation, using nine AIMs (AT3-I/D, APO, SB19.3, PV92, FYnull, LPL, CKMM, GC-F and GC-S) and six genes relate to pigmentation (SCL45A2, SCL24A5, MC1R, OCA2, TYR, ASIP) in two Amerindian tribes from North of Brazil,Tiriyó and Waiampi; urban samples of African descents from Salvador and European and Japanese descents from Ribeirão Preto,SP. The results show that allele frequencies of all markers found in blacks and whites were similar to those in European and African populations and the estimation of admixture with AIMs presents greater African contribution (71%) and European (86%), respectively; which was also observed with the pigmentation markers (99% of European contribution in whites and 66% of African contribution in blacks). The analysis in the Japanese showed allelic frequencies different from the Amerindians and the Amerindian/ Asian contribution observed were 81% with the AIMs and 86% with the pigmentation markers. Among the Amerindians from Tiriyó and Waiampi was observed low contribution of non- Amerindian populations in the admixture estimation with AIMs and even no admixture when used markers of pigmentation, suggesting that, despite the intense process of admixture occurred in Brazil, some tribes still present a homogeneous genetic profile and, preserve the ancestors’ characteristics. The ancestry estimation with markers of skin pigmentation in admixed individuals from Bahia showed high levels of European and Amerindian ancestry contribution compared with the African contribution, which had been the most significant in studies with AIMs, but when analyzed the genotypic distribution of pigmentation markers’ between admixed individuals phenotypically classified as white, mulatto and black, it can be observed that the most frequent allele in Europeans and Africans were in homozygosity among blacks and whites, confirming published data that show the involvement of these markers in mechanisms that determinate the skin pigmentation in different ethnic groups, but also suggest that these markers are not useful tools to define ancestry in admixed populations.

Doenças cardiovasculares (DCVs) são a principal causa de morbidade e mortalidade no mundo e a etnia do indivíduo tem uma importante influência no diagnóstico e tratamento dessas doenças. No entanto, as bases das disparidades étnicas ainda não estão completamente esclarecidas. O estudo de uma população com alta miscigenação genética, fornece potenciais maneiras de compreender a influência genética na determinação de fenótipos de doenças complexas, como as cardiovasculares, em raízes ancestrais comuns. O presente estudo teve como objetivo principal associar etnia auto referida e ancestralidade genética em indivíduos de uma coorte brasileira com fatores de risco para doenças cardiovasculares. Identificamos associação entre etnia auto referida e hipertensão arterial, acidente vascular cerebral (AVC) e hipercolesterolemia. Analisando a hipercolesterolemia com mais detalhes, encontramos associação de etnia com níveis séricos de triglicerídeos (TG), lipoproteína de alta densidade (HDL-c) e índice TG/HDL-c. Essas associações foram fortemente dependentes de confundidores socioeconômicos, mas variações existem na força e direção de cada padrão. No entanto, observamos que o efeito de etnia persistiu mesmo após todas as correções. Em seguida derivamos um painel de marcadores para inferir ancestralidade genética continental, para os componentes ancestrais africano, europeu e ameríndio, e determinamos as proporções de ancestralidade na nossa população de estudo. Na sequência, conduzimos análises de associação entre ancestralidade genética e níveis séricos de lipídios, a fim de estudarmos uma variável menos influenciada por fatores socioeconômicos. Nessas análises encontramos associação entre a ancestralidade ameríndia e níveis séricos de HDL-c. Entender porque essa heterogeneidade existe pode prover importantes pistas sobre as razões para uma importante parte das disparidades étnicas em doenças cardiovasculares / Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in the world and ethnicity plays an important influence on diagnosis and treatment of these diseases. However, the basis of these ethnic disparities are not fully understood. Studying a population with a high genetic admixture allows potential ways to understand the genetic influence on determination of complex disease phenotypes, such as cardiovascular, in common ancestral roots. The present study had as main aim associating self-reported ethnicity and genetic ancestry in individuals from a Brazilian cohort which have risk factors for cardiovascular diseases. We identified association between self-reported ethnicity and arterial hypertension, stroke, and hypercholesterolemia. Analyzing hypercholesterolemia more deeply, we found association of ethnicity with serum levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-c), and TG/HDL-c index. These associations were strongly dependent on socioeconomic confounders, but there are variations in the strength and direction of each pattern. However, we observed that the ethnicity effect persisted even after all adjustments. Following, we derived a panel of markers to infer continental genetic ancestry for African, European and Amerindian ancestral components, and we have determined the ancestral proportions of ancestry in our study population. After that, we conducted association analysis between genetic ancestry and lipids serum levels, in order to study a variable which is less influenced by socioeconomic factors. In these analyzes we found association between Amerindian ancestry and serum levels of HDL-c. Understanding why there is this heterogeneity can provide important clues about the reason for an important part of ethnic disparities in cardiovascular diseases

The purpose of this study is to understand what future role archive institutions have for genealogists as a result of genetic ancestry testing. To answer the purpose of this study, three additional research questions have been given. The research questions are as follows (1) what type of information genealogists search for when using genetic ancestry testing (2) what kind of information genealogists are able to retrieve by performing a genetic ancestry test (3) how the archive institutions perceive genealogists who perform genetic ancestry testing. Three different methods have been used to retrieve relevant source material. The methods used are netnography, introspective action research and interviews. The source material has been retrieved by analysing three different discussion forums, interviewing representatives of archive institutions as well as performing genetic ancestry testing ourselves. The theories used in the analyses is based on the theoretical framework established by Martin Saar that involves three dimensions of genealogy, and a secondary framework based on Lisa M. Givens and Donald O. Case’s particular understanding of information behaviour, as well as information seeking. The results of the study have enabled us to conclude three different future scenarios on how the archive institution’s role for genealogists will change. The first conclusion is that the DNA-services will slowly phase out the primary role archives play for the genealogists today. Instead, the commercial DNA-services will become the primary source of information. The second conclusion is that the definition of “value” in regard to the material generated by a genealogist will change, and their research will in the future be seen as valuable by the archive institutions. The third and final conclusion is that the archive institutions will begin to facilitate information and knowledge regarding different aspects of genetic ancestry testing, due to demand of archival users. This is a two-year master’s thesis in Archival Science.

No / Initiation of breast feeding and duration of any breast feeding are known to differ by ethnic group, but there are limited data on differences in exclusive breast feeding. This study aimed to determine if there are ethnic differences in the initiation and duration of any and exclusive breast feeding. METHODS: Breast-feeding data were obtained from a subsample of 1365 women recruited to a multi-ethnic cohort study (Born in Bradford) between August 2008 and March 2009. Poisson regression was used to investigate the impact of socio-economic, life style and birth factors on ethnic differences in the prevalence of breast feeding. RESULTS: Compared with white British mothers, initiation of breast feeding was significantly higher in all ethnic groups and this persisted after adjustment for socio-economic, life style and birth factors [Pakistani: prevalence rate ratio (PRR) = 1.19 (95% confidence interval 1.10, 1.29); Other South Asian: PRR = 1.29 (1.18, 1.42); Other ethnicities: PRR = 1.33 (1.21, 1.46)]. There were no differences in exclusive breast feeding at 4 months [Pakistani: PRR = 0.77 (0.54, 1.09); Other South Asian: PRR = 1.55 (0.99, 2.43); Other ethnicities: PRR = 1.50 (0.88, 2.56)]. Any breast feeding at 4 months was significantly higher in mothers of all non-white British ethnicities [Pakistani: PRR = 1.27 (1.02, 1.58); Other South Asian: PRR = 1.99 (1.52, 2.62); Other ethnicities: 2.45 (1.86, 3.21)]. CONCLUSIONS: Whilst women of ethnic minority groups were significantly more likely to initiate breast feeding and continue any breast feeding for 4 months compared with white British women, the rates of exclusive breast feeding at 4 months were not significantly different once socio-economic, life style and birth factors were accounted for.

Backgrounds and aims. Insomnia is a common sleep problem with significant health burden to individuals, families and society. Several risk factors contributed to the development of insomnia with significant familial aggregation phenomenon. According to this prospective study, we aimed to (1) explore the longitudinal course and outcomes of insomnia in both children and their parents; (2) confirm the familial aggregation and heritability of insomnia by detailed clinical interviews; (3) explore the potential biological markers of insomnia in terms of heart rate variability, 24-hour urinary cortisol and serial salivary cortisol. / Conclusions. Insomnia is commonly found in both adolescents and adults with moderate persistence rate after 5 years in Hong Kong Chinese. Our findings of increased risk of chronic medical burdens and various upper airway inflammatory diseases in both adolescent and adult subjects with insomnia suggested that insomnia requires comprehensive medical attention. Insomnia is a highly heritable disorder with robust familial aggregations, with a heritability of 0.67 for lifetime insomnia. We found gene-environment interaction on the pathogenesis of insomnia. Our findings strongly suggested the necessity of further molecular genetic analysis on insomnia. Daytime HRV, 24-hour urinary cortisol and serial salivary cortisol might not be the reliable biological markers for insomnia. (Abstract shortened by UMI.) / Results. Phase 1. The prevalences of insomnia were 4.5%, 10.8% and 13.9% at baseline and 6.6%, 8.1% and 11.6% at follow-up for children, fathers and mothers respectively. Similar incidence rate of insomnia was found across adolescents, fathers and mothers (6.2%, 5.4% and 6.8% respectively, p>0.05), while highest persistence rate of insomnia was found in mothers (43.8%), followed by fathers (26.9%) and adolescents (14.9%) (mothers vs adolescents OR(95%CI)=4.43(2.22--8.86); mothers vs fathers OR(95%CI) = 2.11(1.31--3.42); fathers vs adolescents OR(95%CI) = 2.17(0.98--4.52)). Insomnia at baseline was significantly associated with frequent episodes of allergic rhinitis, asthma, and laryngopharyngitis and chronic use of medicine at follow-up in adolescents (p&lt;0.05). Insomnia at baseline was also significantly associated with poor medical outcomes in adults, including frequent allergic rhinitis, otitis media, hypertension, arthritis, psychiatric disorders, chronic pain and gastroesophageal reflux disease at follow-up in middle-aged adults (p&lt;0.05). Phase 2 study . The first degree relatives' recurrent rate was higher in those adolescents with insomnia than those adolescents without insomnia (43.9% vs 22.9% for current insomnia and 51.1% vs 28.0% for lifetime insomnia, respectively p&lt;0.001). Genetic analysis showed that the heritabilities were 0.57 +/- 0.19 for current insomnia and 0.67 +/- 0.13 for lifetime insomnia after adjusted for age and gender. There was significant synergistic interaction between parental history of insomnia and life stress on the development of insomnia of offsprings (p=0.002). Insomnia disorder and its severity were also found to correlate with neuroticism personality, psychological distress and poor quality of life. The phenotypic correlations of insomnia with these factors could be mainly explained by genetic component in bivariate genetic analysis. Phase 3 study. (1) Subjective sleep quantity and quality was consistently and negatively correlated with 24-hour urinary cortisol and salivary cortisol levels in adolescents. However, there was no such association in adults. (2) Adolescents with insomnia diagnosis had lower salivary cortisol at 0 minute after waking up (T1) but less decrease in AUCi3 than non-insomniac adolescents. Although there was no difference in serial salivary cortisol between insomniacs and non-insomniacs in adult, insomnia diagnosis interacted with gender on the effects of AC1Ji and salivary cortisol level at 10:00 pm. (3) There was no difference in 24-hour urinary cortisol between insomniacs and non-insomniacs. (4) There were some inconsistent associations of salivary cortisol with objective and subjective sleep parameters between continuous and dichotomized approaches. Fox example, there was no correlation between salivary cortisol and objective sleep measures in adults when using continuous variables, but, short sleepers as defined by objective TIB&le;400 minutes had higher cortisol levels at T1 (13.5+/-7.9 nmol/L vs 11.2+/-5.0 nmol/L) and T2 (14.0+/-6.0 vs 11.5+/-6.2 nmol/L) than their counterparts (TIB>400 minutes). In brief, cortisol (both salivary and urinary samples) level was more likely to be correlated with subjective measures of sleep than objective measures or insomnia diagnosis. In particular, the association predominantly occurred in adolescent group. / Zhang, Jihui. / Adviser: Yun-bwote Wing. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 245-249). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Conclusion. A much higher percentage of narcolepsy and narcolepsy spectrum disorders was identified in our family study than previous reports. Most of the cases were asymptomatic. The shortened MSL and SOREMPs should be regarded as endophenotypes of narcolepsy. Nocturnal sleep variability was found to be associated with a diagnosis of narcolepsy, daytime shortened MSL and SOREMPs among the relatives. Our data was more concordant with a hypothesis of state boundary control/state instability for narcolepsy. Further molecular genotyping with the incorporation of endophenotype concept should be planned. / Introduction. Most familial studies on narcolepsy lacked detailed face-to-face clinical interviews and objective polysomnogram (PSG) and daytime multiple sleep latency test (MSLT) measurements. Our preliminary family study found one relative (2.9%) with narcolepsy and about 30% of the relatives fulfilled the criteria of narcolepsy spectrum disorder (shortened mean sleep latency [MSL] and/or the presence of sleep onset REM periods [SOREMPs]) The aim of this study was to further explore the familial aggregation and transmission pattern in a larger sample of Hong Kong Chinese narcolepsy, all based on detailed face-to-face interviews and objective measurements. / Methods. Thirty-four narcolepsy (with/without cataplexy) patients, one hundred and two relatives of these probands and forty-eight healthy controls were included in the study. All probands, relatives and controls underwent an overnight standard nocturnal PSG and a daytime MSLT on the following day. In addition, each subject also had a detailed clinical interview and completed sleep questionnaires. HLA DQB1*0602 genotyping was performed for 32 probands, 94 relatives and 30 controls. / Results. Seven (6.9%) relatives were diagnosed as narcolepsy with cataplexy and 9 (8.8%) relatives were diagnosed as narcolepsy without cataplexy. 39 (38.2%) had narcolepsy spectrum disorder and 47 (46.1%) were considered to be normal. A very strong familial aggregation of narcolepsy, narcolepsy spectrum disorder with associated features of shortened MSL (&le;8min) and multiple SOREMPs were found in relatives, but not for sleep related hallucinations and sleep paralysis. Cataplexy seemed to breed true with exclusive but a low percentage of occurrence in the relatives of cataplectic-narcoleptic probands when comparing to the non-cataplectic probands (9% v.s. 0%). A close correlation of HLA-DQB1*0602 with cataplexy was found in both probands and their relatives. The narcoleptic relatives had an excess winter-birth when compared to normal relatives. On the other hand, the first-degree relatives of probands born in other seasons rather than winter had a shorter sleep latency in nocturnal sleep and a shorter mean sleep latency in MSLT. Our data suggested a Mendelian recessive model and multiplicative model for the inheritance of narcolepsy and a Mendelian dominant model for narcolepsy spectrum. Subjective questionnaires were unable in differentiating relatives with narcolepsy spectrum disorder from others. Relatives with narcolepsy reported a high rate of irregular sleep-wake patterns with both variable bedtime and nocturnal sleep duration. This nocturnal sleep variability correlated with daytime shortened MSL and SOREMPs among the relatives. In addition, shortened MSL and SOREMPs should be considered as endophenotypes of narcolepsy as they are the intermediate phenotypes that are heritable, state independent, associated with disease in the population and co-segregated with the disease within families. / Chen, Lei. / Adviser: Wing Yun Kwok. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3775. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 59-70). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 46-05, page: 2667. Advisers: Kim Waller; Steven Kelder. Includes bibliographical references.