Aswan Heart Centre - Egyptian Healthy Volunteers (AHC-EHVol)

To define the genotype of a healthy Egyptian cohort as a crucial step in determining the possible clinical implications of mutations detected in patients recruited in the registry.

Study Overview

• Status: Recruiting
• Conditions: Genetic Predisposition to Disease
• Intervention / Treatment: Other: Whole Genome Sequencing to compare healthy volunteers genome with that of cardiomyopathies patients.

Detailed Description

A key objective of the existing Cardiomyopathies project is to develop and validate assays to identify the genetic and molecular determinants of inherited cardiomyopathies in the Egyptian population.

Current sequencing technology has made cost- and time-effective whole exome and whole genome sequencing feasible. In their attempt to make clinically-relevant conclusions, genetecists, clinicians and bioinformaticians are increasingly faced by thousands of polymorphisms and variants, the clinical significance of which requires careful and systematic analysis of a number of factors including location of the mutation within the genome, type of mutation, gene affected and the protein for which it codes, functional importance of the coded protein, segregation within the family as well as frequency of the detected variation in the same population.

The latter step requires defining what constitutes the "genetic norm" (including normal variants) within the reference population. Data for different populations is already available in a number of databases that are accessible to the scientific community to help maximize the public benefit from research. Examples include the Exome Aggregation Consortium (ExAC) - which aggregates exome sequencing data from 60,706 unrelated individuals - and the 1000 Genomes Project which aggregates whole genome sequencing data from 2500 individuals.

However, to be able to confirm novel gene variants in the Egyptian population, data has to be compared to genomes of healthy individuals in the same population.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Yasmine Aguib, PhD; Phone Number: +201092036368; Email: yasmine.aguib@aswanheartcentre.com
• Study Contact Backup: Name: Ahmed Elguindy, MD; Phone Number: +201001615151; Email: ahmed.elguindy@aswanheartcentre.com

Study Locations

• Egypt
  • Aswan, Egypt
    • Recruiting
    • Aswan Heart Centre - Magdi Yacoub Heart Foundation
    • Contact: Ahmed M ElGuindy, MD, MRCP; Phone Number: +201001615151; Email: ahmed_elguindy@hotmail.com
    • Contact: Shehab M Anwer, MD; Phone Number: +41788816333; Email: shehabanwer@gmail.com
    • Principal Investigator: Magdi H Yacoub, OM FRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1000 adult Egyptian citizen subjects that considers themselves free of cardiovascular disease.

Description

• Inclusion Criteria:

  • Any adult Egyptian citizen subject that considers him/herself free of cardiovascular disease.

• Exclusion Criteria:

  • Individuals under 18 years of age
  • Known cardiovascular disease
  • Known collagen vascular disease
  • Individuals with communication difficulties, or who do not wish to participate
  • Pregnancy
  • Contraindication to MRI
  • Family history of sudden death
  • Family history of a familial cardiomyopathy
  • Family history of premature coronary artery disease (males <40 years, females <50 years).

• Withdrawal Criteria:

  • Withdrawal of consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; Healthy Egyptian individuals to provide the first of its kind resource on human genetic variation in Egyptians, which is essential for understanding the significance of detected variations in patients with inherited cardiovascular disease and their families.	Other: Whole Genome Sequencing to compare healthy volunteers genome with that of cardiomyopathies patients.; Egyptian patients and their family members diagnosed with different types hereditary cardiomyopathies.Healthy Egyptian individuals to provide the first of its kind resource on human genetic variation in Egyptians, which is essential for understanding the significance of detected variations in patients with inherited cardiovascular disease and their families.
Cases; Egyptian patients and their family members diagnosed with different types hereditary cardiomyopathies.	Other: Whole Genome Sequencing to compare healthy volunteers genome with that of cardiomyopathies patients.; Egyptian patients and their family members diagnosed with different types hereditary cardiomyopathies.Healthy Egyptian individuals to provide the first of its kind resource on human genetic variation in Egyptians, which is essential for understanding the significance of detected variations in patients with inherited cardiovascular disease and their families.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Human genetic variation in Egyptians	To perform whole exome sequencing in 1000 healthy Egyptian individuals to provide the first of its kind resource on human genetic variation in Egyptians, which is essential for understanding the significance of detected variations in patients with inherited cardiovascular disease and their families.	10 years

Collaborators and Investigators

• Sponsor: Magdi Yacoub Heart Foundation
• Investigators: Principal Investigator: Magdi H Yacoub, FRS OM, Imperial College London, and Magdi Yacoub Heart Foundation

Publications and helpful links

General Publications

• 1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR. A global reference for human genetic variation. Nature. 2015 Oct 1;526(7571):68-74. doi: 10.1038/nature15393.
• Tan HL, Hofman N, van Langen IM, van der Wal AC, Wilde AA. Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives. Circulation. 2005 Jul 12;112(2):207-13. doi: 10.1161/CIRCULATIONAHA.104.522581. Epub 2005 Jul 5.
• Lindgren A. Stroke genetics: a review and update. J Stroke. 2014 Sep;16(3):114-23. doi: 10.5853/jos.2014.16.3.114. Epub 2014 Sep 30. Erratum In: J Stroke. 2015 Jan;17(1):91.
• UK10K Consortium, Walter K, Min JL, Huang J, Crooks L, Memari Y, McCarthy S, Perry JR, Xu C, Futema M, Lawson D, Iotchkova V, Schiffels S, Hendricks AE, Danecek P, Li R, Floyd J, Wain LV, Barroso I, Humphries SE, Hurles ME, Zeggini E, Barrett JC, Plagnol V, Richards JB, Greenwood CM, Timpson NJ, Durbin R, Soranzo N. The UK10K project identifies rare variants in health and disease. Nature. 2015 Oct 1;526(7571):82-90. doi: 10.1038/nature14962. Epub 2015 Sep 14.
• Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, Zhang Y, Ye K, Jun G, Fritz MH, Konkel MK, Malhotra A, Stutz AM, Shi X, Casale FP, Chen J, Hormozdiari F, Dayama G, Chen K, Malig M, Chaisson MJP, Walter K, Meiers S, Kashin S, Garrison E, Auton A, Lam HYK, Mu XJ, Alkan C, Antaki D, Bae T, Cerveira E, Chines P, Chong Z, Clarke L, Dal E, Ding L, Emery S, Fan X, Gujral M, Kahveci F, Kidd JM, Kong Y, Lameijer EW, McCarthy S, Flicek P, Gibbs RA, Marth G, Mason CE, Menelaou A, Muzny DM, Nelson BJ, Noor A, Parrish NF, Pendleton M, Quitadamo A, Raeder B, Schadt EE, Romanovitch M, Schlattl A, Sebra R, Shabalin AA, Untergasser A, Walker JA, Wang M, Yu F, Zhang C, Zhang J, Zheng-Bradley X, Zhou W, Zichner T, Sebat J, Batzer MA, McCarroll SA; 1000 Genomes Project Consortium, Mills RE, Gerstein MB, Bashir A, Stegle O, Devine SE, Lee C, Eichler EE, Korbel JO. An integrated map of structural variation in 2,504 human genomes. Nature. 2015 Oct 1;526(7571):75-81. doi: 10.1038/nature15394.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): January 31, 2030

Study Registration Dates

• First Submitted: December 14, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 22, 2022

Study Record Updates

• Last Update Posted (Actual): December 22, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Susceptibility; Genetic Predisposition to Disease
• Other Study ID Numbers: AHC-EHVol

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No