Consanguinity and Susceptibility to Common Diseases
Pp. 75-93 (19)
Hagit N. Baris, Wen-Hann Tan and Gabrielle J. Halpern
Offspring of consanguineous parents have an increased risk for congenital
anomalies and major malformations. This is mainly due to the expression of recessive
diseases, since when the parents share a common ancestor, the offspring are more likely
to inherit the same variant/mutation that originated from their common ancestor.
Although it is well known that offspring of consanguineous parents have an increased
risk for monogenic autosomal recessive diseases, the contribution of parental
consanguinity to the development of common multifactorial diseases is controversial.
Most of the common diseases are multifactorial in etiology, i.e. the disease will
manifest only after the risk factor level, both genetic and environmental, has exceeded a
certain cut-off point. Coronary artery disease (CAD) is caused by numerous genetic and
environmental factors, and a small proportion of cases are due to rare, highly penetrant
variants in single genes. CAD is known to cluster in families, and early-onset CAD has
a particularly strong genetic component. Hypertension is influenced by hundreds of
loci, and consanguinity influences not only the blood pressure levels but also their
reactivity. Asthma is primarily a multifactorial polygenic disease, although it is possible
that homozygous mutations in specific genes may result in the "asthma phenotype".
There are conflicting reports as to whether consanguinity plays a role in the etiology of
diabetes mellitus – some studies have found an association while others have not. A
possible association between consanguinity and psychiatric disorders is explored, and
the possible effect of consanguinity on cancer is also discussed.
Congenital anomalies, consanguineous parents, major malformations,
multifactorial diseases, recessive diseases.
The Genetic Institute, Rambam Health Care Campus, P.O. Box 9602, Haifa, 3109601, Israel.