Multifactorial inheritance Multifactorial inheritance (complex inheritance) (complex inheritance)

Multifactorial inheritance Multifactorial inheritance

(complex inheritance) (complex inheritance)

the inheritance determined by a the inheritance determined by a

combination of multiple genetic and combination of multiple genetic and

environmental factors

environmental factors

 qualitative (present/absent) qualitative (present/absent)

 quantitative (measurable) quantitative (measurable)

– blood presure blood presure – height height

– intelligence intelligence

 does not conform to any recognized does not conform to any recognized pattern of Mendelian inheritance pattern of Mendelian inheritance

 familial aggregation (affected individuals familial aggregation (affected individuals cluster in families)

cluster in families)

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 λ _r for Siblings of Probands with Diseases with Familial Aggregation and Complex Inheritance

Disease Relationship λ

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 the risk is greatest among close relatives of the patient and decreases in more distant relatives

and decreases in more distant relatives

• the incidence of the condition is greatest among the incidence of the condition is greatest among

relatives of the most severely affected patiens

relatives of the most severely affected patiens

• if the condition is more common in one sex, then relatives if the condition is more common in one sex, then relatives of an affected individual of the less frequently affected sex of an affected individual of the less frequently affected sex is at higher risk than relatives of an affected individual of is at higher risk than relatives of an affected individual of

the more frequently affected sex the more frequently affected sex

• if there is more than one affected close relative, then the if there is more than one affected close relative, then the risks for other relatives are increased

risks for other relatives are increased

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

(GWAS/GWLS)

association

linkage

Digenic inheritance