Based on the previous work, a family-based cohort was established and expanded in the rural community of northern China using a bidirectional family-based cohort study design. Proband-based ascertainment was adopted to recruit subjects of the study. Data on medical information of common chronic non-communicable diseases including cardiovascular diseases and kidney diseases, epidemiological features and biological samples were systematically collected through baseline investigation, regular follow-up, and outcome monitoring. All records on the study were under all-electronic management and biological samples were managed with standardized transport, storage, and measurement. Physical examination, medical examination and modern molecular biology technology were adopted during field investigation. Researchers explored the environmental, behavioral and genetic risk factors of common chronic non-communicable diseases such as cardiovascular diseases and kidney diseases with statistical analysis strategy based on longitudinal data and family-based data. Association and linkage analysis was adopted to identify novel loci of these diseases. Gene-environment interaction analysis was also conducted to further explore the etiology of the diseases. Through a comprehensive study of the etiology of these chronic diseases, this family-based cohort will be used to better understand the genetic architecture and environmental risk factors of the common chronic diseases.

  • General Information of Study
    • Overview
      Name Family-based cohort study on common chronic non-communicable diseases in rural areas of northern China (FISSIC: The Fangshan/Family-based Ischemic Stroke Study in China)
      Project Number CCC2017071301
      Website None
      Investigators
      HU Yonghua
      Institutions School of Public Health, Peking University
      Contacts
      HU Yonghua
      Funding Key Project of the National Natural Science Foundation, project number: 81230066; Project of the National Natural Science Foundation, project number: 81473043
      Objectives Based on the previous work, a family-based cohort was established and expanded in the rural community of northern China using a bidirectional family-based cohort study design. Proband-based ascertainment was adopted to recruit subjects of the study. Data on medical information of common chronic non-communicable diseases including cardiovascular diseases and kidney diseases, epidemiological features and biological samples were systematically collected through baseline investigation, regular follow-up, and outcome monitoring. All records on the study were under all-electronic management and biological samples were managed with standardized transport, storage, and measurement. Physical examination, medical examination and modern molecular biology technology were adopted during field investigation. Researchers explored the environmental, behavioral and genetic risk factors of common chronic non-communicable diseases such as cardiovascular diseases and kidney diseases with statistical analysis strategy based on longitudinal data and family-based data. Association and linkage analysis was adopted to identify novel loci of these diseases. Gene-environment interaction analysis was also conducted to further explore the etiology of the diseases. Through a comprehensive study of the etiology of these chronic diseases, this family-based cohort will be used to better understand the genetic architecture and environmental risk factors of the common chronic diseases.
      Start Date 2005/1/1
      End Date 2017/12/1
    • Study Design
      Number of Participants 1,000 stroke pedigree, 2,000 high blood pressure and diabetes pedigree
      Age Range ≥35 years old
      Geographic Distribution Fangshan District, Beijing
      General Information of Study Design and Sample Methods Stroked, diabetic and hypertensive families were recruited in several townships in Fangshan District, Beijing. Researchers took proband-initiated contact method to recruit the subject who was proband with cardiovascular disease in his/her family. Then researchers collected information about the family members including the biological parents and the siblings.
      Inclusion Criteria The inclusion criteria for the proband include:
      1. Age >=35 years old,
      2. Permanent residents who have been living in Fangshan district for more than 5 years,
      3. With stroke diagnosed by CT or MRI in secondary-level or above clinical hospitals,
      4. At least one surviving parent or sibling is willing to participate in this study,
      5. Written signed informed consent, having no major defect, able to cooperate with the investigation and physical examination.
      The inclusion criteria for relatives include:
      1 Age >=35 years old,
      2.Parents who have biological parent-child relation with probands,
      3.Whole siblings of the proband,
      4 Relatives with stroke also need to have CT or MRI diagnosis in secondary-above clinical hospitals while relatives without stroke need to be verified by non-stroke state confirmation questionnaires,
      5 Written signed informed consent, no major defects, able to cooperate with the investigation and physical examination.

      Exclusion Criteria The criteria for the exclusion of the proband include:
      1. Without CT or MRI diagnosis of stroke,
      2. With stroke included in single gene disorder,
      3. Unable to participate in the investigation due to removal, death or serious physical and psychological deficiencies.
      The exclusion criteria for relatives include:
      1. Relatives with stroke without CT or MRI diagnosis,
      2. Unable to participate in the investigation and physical examination due to major defects or other reasons,
      3. Relatives other than parents, siblings, children and spouses.

    • Other Information
      Key Achievements Up to now, the stroke, diabetes, and hypertension families collected through the cohort studies have met the sample size need. Apart from the general demographic characteristics and the environmental risk factors, they also have received a series of detailed blood biochemical tests and physical examinations, including ankle brachial index, body fat index, carotid ultrasonography and pulse wave velocity. In addition, the studies have tested a total of 121 SNP loci. Up to now, in total 27 articles have been published in Chinese or English journals, including 14 SCI papers.
      Marker Papers 1. Wang L, Gao P, Zhang M, Huang Z, Zhang D, Deng Q, Li Y, Zhao Z, Qin X, Jin D, Zhou M, Tang X, Hu Y, Wang L. Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013. JAMA. 2017;317(24):2515-2523. doi:10.1001/jama.2017.7596
      2. Sun K, Song J, Liu K, Fang K, Wang L, Wang X, Li J, Tang X, Wu Y, Qin X, Wu T, Gao P, Chen D, Hu Y. Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: a Chinese sib pair study. Journal of thrombosis and thrombolysis. 2017 43(3):401-410.
      3. Cao Y, Sun K, Xiang X, Liu Z, Juan J, Yang C, Qian J, Yang C, Song J, Huang S, Liu X, Li N, Tang X, Li J, Wu T, Chen D , Hu Y. Analysis on relationship between glycemic control and intima-media thickness of carotid artery in patients with type 2 diabetes mellitus [J]. Chinese Journal of Disease Control and Prevention. 2016,20(07):647-651. (in Chinese)
      4. Sun K, Xiang X, Li N, Huang S, Qin X, Wu Y, Tang X, Gao P, Li J, Wu T, Chen D, Hu Y. Gene-Diet Interaction between SIRT6 and Soybean Intake for Different Levels of Pulse Wave Velocity. Int J Mol Sci. 2015 Jun16(7):14338-14352.
      5. Tang X, Laskowitz DT, He L, Ostbye T, Bettger JP, Cao Y, Li N, Li J, Zhang Z, Liu J, Yu L, Xu H, Hu Y. Goldstein, L. B.. Neighborhood socioeconomic status and the prevalence of stroke and coronary heart disease in rural China: a population-based study. International journal of stroke : official journal of the International Stroke Society. 2015 Aug 10(3):388-395.
      6. Sun K, Liu Z, Cao Y, Juan J, Xiang X, Yang C, Huang S, Liu X, Li N, Tang X, Li J, Wu T, Chen D, Hu Y. The relationship between blood glucose control and the velocity of brachial ankle pulse wave in patients with type 2 diabetes mellitus in a community in Beijing [J]. Journal of Peking University (Health Sciences). 2015,47(03):431-436. (in Chinese)
      7. Li S, Fang K, Wang W, Hu Y, Chen D. Gene-environment interaction among GSTT1, PON2 polymorphisms and organic solvents on gestational age in a Chinese women cohort. Journal of assisted reproduction and genetics. 2014 May 31(7):881-888.
      8. Liu K, He L, Tang X, Wang J, Li N, Wu Y, Marshall R, Li J, Zhang Z, Liu J, Xu H, Yu L, Hu Y.Relationship between menopause and health-related quality of life in middle-aged Chinese women: a cross-sectional study. BMC women's health. 2014 Jan 14:7.
      9. Wu N, Tang X, Wu Y, Qin X, He L, Wang J, Li N, Li J, Zhang Z, Dou H, Liu J, Yu L, Xu H, Zhang J, Hu Y, Iso H. Cohort profile: the Fangshan Cohort Study of cardiovascular epidemiology in Beijing, China. Journal of epidemiology. 2014 Nov 24(1):84-93.
      10. Zhu Y, Liu K, Tang X, Wang J, Yu Z, Wu Y, Chen D, Wang X, Fang K, Li N, Huang S, Hu Y. Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based case-control study. Journal of thrombosis and thrombolysis. 2014 Mar 38(4):470-476.

      Strength Family-based study design could avoid the impact of population stratification as well as stress the role of family history. Therefore, it is more applicable to verify the genetic basis of the diseases. Meanwhile, evaluating environmental risk factors among family members with similar genetic background is helpful to elucidate gene-environment interactions. Cohort study can help monitor incident cases and long-term observation makes higher penetrance of the genotypes, which undoubtedly increase the accuracy of the study. In addition, long-term cohort study can monitor changes of the individual environmental risk factors, and better control the environmental confunders during genetic etiology exploration thus to improve research effectiveness.
      Weakness One great limitation of the study is that the recruiting and follow-up of the study subjects were affected by local mass coordination, population mobility, family members not residing in local areas and other issues. In addition, the difficulty in data analysis and interpretation due to the relevance of members within the family should also be considered.