Genetics of Common Complex Diseases 2022 PDF

Royal College of Surgeons in Ireland Medical University of Bahrain Genetics of common, complex disease Salim Fredericks Learning objectives Explain multifactorial inheritance Compare and contrast the features of common and rare diseases Describe approaches to mapping genetic factors...

Royal College of Surgeons in Ireland Medical University of Bahrain Genetics of common, complex disease Salim Fredericks Learning objectives Explain multifactorial inheritance Compare and contrast the features of common and rare diseases Describe approaches to mapping genetic factors influencing common diseases (i.e. GWAS design) Discuss the genetics of common disease, illustrate with an example disease Human inherited disease Some diseases are caused by genetic (ie: DNA) defects disease genotype --- > disease phenotype Two broad categories: 1. Single-gene (monogenic) defects single disease allele, dominant or recessive simple Mendelian inheritance pattern 2. Multi-gene (polygenic) defects interactions of several genes complex (ie: non-Mendelian) inheritance  04_06.jpg Disease Expression?  What do we mean by a ‘rare disease’? A disease with an prevalence of less than 1/2000. Often (but not always) governed by a single gene/locus. They are often chronic and life threatening They are often early onset – affecting children Estimated that 5,000-7,000 rare diseases exist Collectively, rare diseases are common. Estimated that 6-8% of the population are affected by a rare disease. Examples: – Neurofibromatosis – Huntington’s disease – Phenylketonuria – Sickle-cell anemia (depends on region – in EU 1/160,00, higher in Bahrain) – Etc (see examples from Mendelian disease lectures..) What do we mean by a common disease? Commonly occurring in a population Polygenic or multifactorial in nature. Can be chronic Onset is often later in life Pretty much everyone is affected by a common disease at some point in their life. Examples: – cancers – obesity – hypertension – diabetes – Etc Monogenic/polygenic/ multifactorial Presence or absence of Presence or absence of phenotype Presence of absence of phenotype phenotype depends on depends on genotypes across depends on interaction of genes genotype at a single locus several loci and environment (but all risk is attributable to genes) Polygenic (>2genes) DMD Scurvy  Common vs rare disease Common Rare Prevalence Very common 1 Genotype associated with higher odds of outcome – OR