CHGA genetic variation: Risk factor for hypertensive ESRD in blacks
Estimator of RR: Odds ratio (OR). Given a risk factor, OR = (have trait/do not have trait).
WHAT IS A ÒCOMPLEX TRAITÓ?
Trait = phenotype.
Disease causation/etiology/origin: The old conundrum of: ÒNature (heredity) versus nurture (environment)Ó. How to solve this riddle: Family/pedigree or twin studies (see below).
Gene3
Common environment
Polygenic background
APPROACHES TO COMPLEX TRAITS.
(Genetic) epide miology. Demographics (age, sex, ethnicity, geography, fam hx). ÒRiskÓ (susceptibility) factors (see above). Relative risk (RR): Given a risk factor, what is the increase in trait
PURPOSE. In the next two hours, we plan to cover the role of heredity and genes in
very common, non-Mendelian traits that are frequently seen by primary care physicians. We will illustrate how we establish the role of heredity on any trait, and then methods to position the particular genes that influence such a trait.
3
3
7
20
6
2
2
5
15
4 3
10
1
1
2
5
1
0
0
0
0
Complex Trait Modege
Gene1
disequilibrium
Linkage Association
Mode of inheritance
Gene2
Disease Phenotype
Individual environment
prevalence? Estimator of RR: Odds ratio (OR). Given a risk factor, OR = (have trait/do
not have trait). OR +/- confidence interval (+/-95% CI) versus reference (no risk) =1. No risk: RR or OR = 1. OR +/- CI >>1 Risk (susceptibility) factor. OR +/- CI <<1 Protective factor. Test by 2 (2x2 contingency table).
Frequency. Most (>95%) of the disease encountered in internal medicine, family
medicine, pediatrics, neurology, or psychiatry is complex, and its origin is not well understood. Not clearly completely hereditary (Mendelian) or environmental. Read: Hypertension, coronary artery disease, arrhythmia, stroke, aneurysm, asthma, COPD, diabetes, obesity, schizophrenia, bipolar disorder . . .
get the trait. Some people who do not have the gene still get the trait.
Bimodality: Hallmark of a major gene effect on a quantitative trait.
Bimodality: Hallmark of a major gene effect on a quantitative trait.
Gene tics of comple x human dise ase traits. Daniel T. OÕConnor, M.D. Department of Medicine. Nopm-252. First year curriculum in human genetics. Wed Apr 1, 2009. CMME-2047.
Polygenic Traits
1 Gene
3 Genotypes 3 Phenotypes
2 Genes
9 Genotypes 5 Phenotypes
3 Genes
27 Genotypes 7 Phenotypes
4 Genes
81 Genotypes 9 Phenotypes
Multifactorial: Genes, environment, gene-by-environment interactions.
Non-Me nde lian. Mendelian: Gene Trait (1:1; high penetrance ~100%). Non-Mendelian: Only partial penetrance. Some people with the gene do not