Sleep time and sleep-related symptoms across two generations – results of the community-based RHINE and RHINESSA studies

Study objectivesTo analyze the association between sleep-related symptoms and sleep length in parents and their children in relation to other risk factors in both generations.MethodThe participants were parents (n = 5,855, age 54.3 ± 6.5 years, 45.2% men) who participated in the community-based Respiratory Health in Northern Europe (RHINE) study and one random member of their adult offspring (n = 5,855, age 30.2 ± 7.7 years, 41.5% men) who participated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study. Both generations responded to identical questionnaires on sleep symptoms, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), snoring, nocturnal sweating, nocturnal gastroesophageal reflux (nGER), sleep time and excessive daytime sleepiness (EDS). Insomnia was defined as either, or both, DIS and DMS in combination with EDS.ResultsAll sleep variables except nocturnal sweating were more common in offspring whose parents had reported the same symptom. After adjusting for age, gender, BMI, smoking, physical activity, education, center and parents' total number of children, there were independent associations between sleep symptoms in parents and offspring for DIS (adj. OR, 95% CI: 1.52, 1.20–1.93), DMS (1.34, 1.15–1.56), snoring (1.45, 1.15,1.83), nGER (1.65, 1.15–2.37), insomnia (1.39, 1.13–1.73), short sleep time (<6 h/night) (2.51, 1.72–3.68) and EDS (1.48, 1.26,1.72). There were no independent relationships between symptoms in parents and offspring for EMA, nocturnal sweating or long sleep time (>9 h/night).ConclusionThe familiar aggregation of many sleep disturbances was not explained by investigated lifestyle and environmental factors. This supports a heritable factor in sleep problems.     

Some personality traits converge gradually by long-term partnership through the lifecourse – Genetic and environmental structure of Cloninger's temperament and character dimensions

Temperament and Character Inventory (TCI) is a comprehensive personality inventory that is widely used in behavioral genetics. The original theory suggested that temperament traits were under genetic influences, whereas character traits were gradually built by an interaction between temperaments and environment until early adulthood. This study attempted to evaluate TCI by examining the genetic and environmental contributions to personality with particular attention to spousal effects. From 687 families, a total of 3459 Korean adult individuals completed the survey. Among them, there were 542 Monozygotic (MZ) twin pairs and 122 Dizygotic twin pairs. Intraclass correlation coefficients (ICCs) and heritability were calculated to examine the genetic and shared environmental contributions to personality. Moderate genetic contributions (0.17–0.43) were found for all TCI traits along with the evidence of shared environment (0.11–0.31) for harm avoidance (HA) and all characters. The ICCs of TCI in MZ pairs ranged 0.36–0.46. Spouses' had little resemblance for temperament, whereas for character dimensions, spouses (0.27–0.38) were more similar than first degree relatives (0.10–0.29). Resemblance between spouses increased with duration of marriage for most characters and HA. When the growing similarities between spouses were compared with their MZ cotwins' for subgroup of 81 trios, self-directedness (SD) of character showed even more similarities toward their spouses than cotwins as partnership duration increased (r = 0.32). Our findings with regard to change in SD into late adulthood support the psychobiological theory of temperament and character, which suggests that both personality domains have distinct developmental trajectories despite equally large genetic influences.     

青少年和儿童牙冠与牙弓遗传度的研究

错畸形的病因学研究是口腔正畸学的热点之一。错畸形多具有遗传倾向,表现为亲代与子代之间牙及颅面性状的相似性,牙齿发育作为全身发育的一部分,环境因素可以通过影响基因的表型而使牙齿发育表现多种多样,但牙齿发育受遗传因素影响更大[1]。牙冠宽度是牙齿形态测量及牙量指数的重要指标,牙弓形状、大小与牙弓间隙分析、矫治后牙弓的稳定性密切相关。牙冠和牙弓的测量值在正畸诊断和治疗中具有重要意义。该文对遗传性因素影响牙齿和牙弓正常发育的研究现状进行概述,以期为错畸形的临床诊断和治疗提供参考。     

西安市30~36月龄幼儿肥胖遗传度及4个SNPs位点多态性分析

目的 分析西安市30~36月龄幼儿肥胖遗传度，探讨4个与体重指数相关的基因单核苷酸多态性（SNPs）位点在幼儿肥胖易感性中的作用。方法 选取2017年3月至2018年12月在西安市随机抽样的4个社区的30~36月龄幼儿1 637例为研究对象，对幼儿行体格测评，对家长进行问卷调查，用Falconer回归法计算幼儿肥胖的遗传度。共收集到297例行血生化检查幼儿的静脉血样本，其中肥胖/超重儿140例（肥胖/超重组），正常体重儿157例（正常体重组）。应用MassARRAY RS1000分型技术对CDKAL1基因rs2206734、KLF9基因rs11142387、PCSK1基因rs261967和GP2基因rs12597579位点进行检测，比较肥胖/超重组与正常体重组幼儿等位基因、基因型的分布差异，进一步用非条件logistic回归模型分析显性、隐性遗传模型效益。结果 1 637例幼儿中，肥胖双亲的遗传度为83%±8%，源于母亲的遗传度为86%±11%，略高于源于父亲的78%±12%。rs2206734位点等位基因和基因型、rs261967位点基因型分布在肥胖/超重组和正常体重组幼儿间比较差异有统计学意义（P < 0.0125）；rs2206734携带T等位基因的个体肥胖的风险低于纯合子CC个体（OR=0.24，P < 0.0125）；rs261967纯合子GG个体肥胖的风险显著高于携带A等位基因的个体（OR=4.11，P < 0.0125）。结论 遗传因素在幼儿肥胖发病中起重要作用；CDKAL1基因rs2206734和PCSK1基因rs261967位点SNPs和西安市30~36月龄幼儿肥胖易感性相关。     

Using GWAS to identify genetic predisposition in hepatic autoimmunity

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major hepatic autoimmune conditions. Patient morbidity and mortality remain high across these three diseases, and an unmet need for rational therapy exists. Disease understanding has focused on combining clinical and laboratory based science to provide better insights into the joint host and environmental factors necessary for the initiation, and perpetuation, of hepato-biliary inflammation. Twin studies, family studies, population studies and an inter-relationship with other autoimmune phenomena suggest a genetic component to risk for each disease. Until recently, understanding of this genetic risk has been limited to HLA haplotypes. Associations with risk-conferring and protective HLA haplotypes are present in all three diseases. Over the last few years, genome-wide association studies (GWAS), and related genetic association studies, have greatly increased understanding of the genetic risk signature of these three diseases and autoimmunity in general. Here we consider the rationale for GWAS in general and with specific reference to hepatic autoimmunity. We consider the process of GWAS, and highlight major findings to date. Potential functional implications of key findings are discussed including the IL-12/STAT4 pathway in PBC and the CD28/IL-2 pathway in PSC. We describe the marked pleiotropy demonstrated by PBC and PSC, which is consistent with other autoimmune diseases. Further, we focus on specific gene associations including SH2B3, which is common to all three diseases, and FUT2 in PSC, which represents a link between environment and genetics. We review attempts to translate GWAS findings into basic laboratory models including in vivo systems and highlight where clinical observations relate to genetics. Finally we describe deficiencies in GWAS to date and consider future study of genetics in hepatic autoimmunity.     

Evidence for genetic regulation of endothelial progenitor cells and their role as biological markers of atherosclerotic susceptibility.

AIMS: Endothelial progenitor cells (EPCs) are found in the peripheral circulation and are capable of endothelial repair and neovascularization. EPC number and function are reduced in subjects with cardiovascular risk factors or proven coronary artery disease (CAD). We hypothesized that EPC number and/or function may be genetically regulated and may vary in healthy adult offspring depending on parental history of CAD. METHODS AND RESULTS: We studied 102 subjects comprising 24 healthy parent-healthy offspring pairs and 27 CAD parent-healthy offspring pairs. We measured the number of circulating CD34(+)VEGFR-2(+) and AC133(+)VEGFR-2(+) EPCs, the number of EPCs grown in culture, and the migration capacity of cultured EPCs towards vascular endothelial growth factor. There was significant correlation in the number of cultured EPCs between healthy parents and their offspring (R = 0.492, P = 0.015) and CAD parents and their offspring (R = 0.751, P < 0.001). Offspring of subjects with CAD had significantly higher numbers of circulating CD34(+)VEGFR-2(+) and AC133(+)VEGFR-2(+) cells (P = 0.018 and P < 0.001, respectively). There was no difference in migration capacity between groups. CONCLUSION: Our results suggest that EPC number is, at least in part, genetically regulated. Circulating EPCs may represent biological markers of occult vascular damage in offspring with hereditary risk of CAD.     

青岛和丽水地区双生子研究：体育活动和静坐行为的遗传度

目的 探讨山东省青岛和浙江省丽水地区双生子人群体育活动和静坐行为的遗传度。方法 使用两地区2004 年随访的有卵型信息的双生子人群（共568 对,其中青岛242 对,丽水326 对）横断面调查资料,通过问卷调查得到体育活动和静坐行为信息。采用基于双生子的方差组分分析方法计算双生子表型的遗传度。结果 同卵双生子有367 对,异卵双生子有201 对,双生子中男性571 人,女性565 人。同卵双生子年龄为（41.14±10.11）岁,异卵双生子年龄为（41.23±9.89）岁。青岛和丽水地区＜40 岁人群的体育活动遗传度为78%（35%～96%）、59%（0～94%）,≥40 岁人群体育活动不受遗传影响。青岛和丽水地区静坐行为遗传度分别为68%（59%～75%）、32%（7%～62%）。结论 青岛和丽水地区人群静坐行为水平受遗传影响,且遗传因素在20～40 岁人群的体育活动水平中有着重要作用。     

骨性安氏Ⅲ类错(牙合)患者亲子间颅颌面形态的遗传度研究

目的通过对骨性安氏Ⅲ类错（牙合）亲子之间的不同颅颌面结构的遗传度研究,探讨遗传因素在骨性安氏Ⅲ类错（牙合）发病中的作用。方法对65例骨性安氏Ⅲ类错（牙合）患者及其父母拍摄头颅侧位片,选取29个测量标志点,26个测量项目,分别用均父母-子代回归系数法和单亲一子代回归系数法估算不同测量项目的遗传度。结果均父母-子代回归系数法显示,亲子之间颅骨、上下颌骨有很高的遗传度,达到70％～90％,角度的遗传度高于线距的遗传度,代表牙齿和软组织的大部分测量项目的遗传度都在30％-40％左右。单亲．子代回归系数法显示,硬组织和软组织中母子的遗传度大于父子的遗传度,性别在亲子间的遗传有一定的影响。结论亲代的颅颌面结构特征在一定程度上可以预测子代颌骨的生长发育。