the Relative Contributions of Genes and Environment to Complex Disease

CL(P), Cleft lip with or without cleft palate.

Another approach is to compare the disease relative risk ratio in biological relatives of the proband with that in biologically unrelated family members (e.g., adoptees or spouses), all living in the same household environment. Returning to MS, for example, λr is 190 for MZ twins and 20 to 40 for first-degree biological relatives (parents, children, and sibs). In contrast, λr is 1 for the adopted siblings of an affected individual, suggesting that most of the familial aggregation in MS is genetic rather than the result of a shared environment. A similar analysis can be carried out for quantitative traits such as blood pressure: no correlation exists between a child’s blood pressure and that of his adopted siblings, in contrast to the positive correlation with blood pressure of biological siblings, all living in the same household.

Distinguishing between Genetic and Environmental Influences Using Twin Studies


In contrast, DZ twins arise from the simultaneous fertilization of two eggs by two sperm; genetically, DZ twins are siblings who share a womb and, like all siblings, share, on average, 50% of the alleles at all loci. DZ twins are of the same sex half the time and of opposite sex the other half. In contrast to MZ twins, DZ twins occur with a frequency that varies as much as fivefold in different populations, from a low of 0.2% among Asians to more than 1% of births in parts of Africa and among African Americans.

The striking difference between MZ and DZ twins in their genetic makeup is most easily seen by comparing the pattern for a type of so-called DNA fingerprint in twins (Fig. 8-4). This method of DNA fingerprinting is generated by simultaneously examining many DNA fragments of varying lengths that share a particular DNA sequence (minisatellite) and are located throughout the genome. MZ twins show an indistinguishable pattern, whereas many differences are seen between DZ twins, whether of same sex or not.


Figure 8-4 DNA fingerprinting of twins by detecting a variable number tandem repeat polymorphism, a class of polymorphism that has many alleles in loci around the genome due to variation in the number of copies repeated in tandem (see Chapter 4). Each pair of lanes contains DNA from a set of twins. The twins of the first and third sets have identical DNA fingerprints, indicating that they are identical (MZ) twins. The twins of the set in the middle have clearly distinguishable DNA fingerprints, confirming that they are fraternal (DZ) twins. See Sources & Acknowledgments.

Disease Concordance in Monozygotic and Dizygotic Twins

MZ and same-sex DZ twins share a common intrauterine environment and sex and are usually reared together in the same household by the same parents. Thus a comparison of concordance for a disease between MZ and same-sex DZ twins shows how frequently disease occurs when relatives who experience the same prenatal and often the same postnatal environment have the same alleles at every locus (MZ twins), compared with only 50% of their alleles in common (DZ twins). Greater concordance in MZ versus DZ twins is strong evidence of a genetic component to the disease, as shown in Table 8-4 for a number of disorders.


Concordance Rates in MZ and DZ Twins for Various Multifactorial Disorders

Concordance (%)*
Disorder MZ DZ
Nontraumatic epilepsy 70 6
Multiple sclerosis 18 2
Type 1 diabetes 40 5
Schizophrenia 46 15
Bipolar disease 62 8
Osteoarthritis 32 16
Rheumatoid arthritis 12 3
Psoriasis 72 15
Cleft lip with or without cleft palate 30 2
Systemic lupus erythematosus 22 0
Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on the Relative Contributions of Genes and Environment to Complex Disease
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