Multifactorial Inheritance Flashcards
Frequency of multifactorial disease
5% incidence at birth
60% population prevalence
Examples of multifactorial congenital malformations
Cleft lip and palate
Neural tube defects
Heart defects
Examples of multifactorial adult-onset diseases
Diabetes
Heart disease
Epilepsy
Affective Disorders
Examples of multifactorial traits in general population
Height
Intelligence
Blood pressure
Genetics factors involved in multifactorial inheritance
Susceptibility genes
Modified genes
Epigenetic modifications
Environmental factors in multifactorial conditions
Diet
Exercise
Teratogens
Infections
Smoking
Trauma
Stress
Pollutants
Continuous multifactorial traits
Quantitative traits
Bell shaped distribution (example: height)
Discontinuous multifactorial traits
Qualitative traits
Threshold effect
Trait is present or absent (example: CHD)
Twin studies
Probability that one twin will have a trait given that the other twin has the trait
Large difference in concordance between monozygotic (MZ) and dizygotic (DZ)
Concordance rates for MZ twins for
Epilepsy
Diabetes type I
Schizophrenia
Cleft lip +/- cleft palate
70
40
53
30
Concordance rates for DZ twins for
Epilepsy
Diabetes type I
Schizophrenia
Cleft lip +/- cleft palate
6
4.8
15
5
Liability
genetic and environmental factors involved in the occurrence of a MF tait
What model can explain the presentation of discontinuous traits
Threshold
Correlation
Tendency for values of a physiological measurement to be more similar among relatives than among general population
Heritability
Fraction of the total phenotypic variance of a quantitative trait caused by genes
Candidate gene studies
disease association studies
Sibling pairs
Multifactorial inheritance recurrence risks
Based on empiric data
Risk to first degree relatives is often ~2-5%
Depends on number of affected relatives and degree of relatedness
RR to 1st degree relatives is increased above general population risk
RR increases proportionately to the number of affected individuals in family
RR typically higher if disorder is in the more severe range of the phenotype
RR is higher if the proband is of the less commonly affected sex
RR quoted are averages
RR can vary on population
Population incidence of cleft palate per 1000
.4
Population incidence of cleft palate +/- CP per 1000
.4-1.7
Population incidence of hip dysplasia per 1000
2
Population incidence of CHD per 1000
1.7
Population incidence of neural tube defects per 1000
2-10
Population incidence of pyloric stenosis per 1000
1 (female), 5 (male)
Pyloric stenosis
narrowing of pylorus
More common in males
Higher liability in females (stronger genetic and environmental factors needed to cross threshold)
Pyloric stenosis recurrence risk
affected female - RR higher for male first degree relatives than female
Half siblings are what degree of relatives
2nd
What increases recurrence risk for multifactorial inheritance
Close relationship to proband
High heritability
Multiple affected relatives
Severe form or early onset
Proband is the less frequently affected gender
Population risk of CL/P
1:500-1000
Native Americans: 3.6/1000 (1/277)
Japanese: 1/476
Chinese: 1/714
White: 1/1000
Black: 1/3333
