Multifactorial inheritance complex inheritance the inheritance determined by

Multifactorial inheritance (complex inheritance) the inheritance determined by a combination of multiple genetic and environmental factors

n qualitative (present/absent) n quantitative (measurable) – – – blood presure height intelligence

does not conform to any recognized pattern of Mendelian inheritance n familial aggregation (affected individuals cluster in families) n

Degree of Relationship and Alleles in Common Relationship to Proband Proportion of Alleles in Common with Proband Monozygotic twin 1 First-degree relative 1/2 Second-degree relative 1/4 Third-degree relative 1/8

Concordance Rates in MZ and DZ Twins Concordance (%) Disorder MZ DZ Nontraumatic epilepsy 70 6 Multiple sclerosis 17. 8 2 Type 1 diabetes 40 4. 8 Schizophrenia 46 15 Bipolar disease 62 8 Osteoarthritis 32 16 Rheumatoid arthritis 12. 3 3. 5 Psoriasis 72 15 Cleft lip with or without cleft palate 30 2 Systemic lupus erythematosus 22 0

Risk Ratios λr for Siblings of Probands with Diseases with Familial Aggregation and Complex Inheritance Disease Relationship λr Schizophrenia Siblings 12 Autism Siblings 150 Manic-depressive (bipolar) disorder Siblings 7 Type 1 diabetes mellitus Siblings 35 Crohn's disease Siblings 25 Multiple sclerosis Siblings 24

• the risk is greatest among close relatives of the patient and decreases in more distant relatives • the incidence of the condition is greatest among relatives of the most severely affected patiens

• if the condition is more common in one sex, then relatives of an affected individual of the less frequently affected sex is at higher risk than relatives of an affected individual of the more frequently affected sex • if there is more than one affected close relative, then the risks for other relatives are increased

n genome wide association/linkage studies (GWAS/GWLS)

association

linkage

Digenic inheritance