MP is criticised for saying that marriage of first cousins is a health problem
BMJ 2005; 331 doi: https://doi.org/10.1136/bmj.331.7528.1292 (Published 01 December 2005) Cite this as: BMJ 2005;331:1292
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Dr. Overall’s general point - that population substructure with a
predilection for mating within widely extended families is a factor at
least comparable to first-cousin marriage in leading to increased numbers
of children with homozygous recessive genetic conditions - looks right.
It convinces me, no population geneticist.
But I would like more examination of this part: “[Benson suggests] …
non-consanguineous marriage may be the only way to lower the risk of
having affected children. This is only true if the recessive variants are
rare. For common variants consanguineous marriage can have a negligible
effect on the risk”.
This can mislead because of the much discussed concern about measures
of risk, at least from a population perspective: the difference between
relative and absolute risk, with the latter being of greater public health
importance.
Some rather crude calculations might make this point. Supposing we
have a population A where all members mate completely at random (this is
not in the least realistic, but is for argument’s sake). Suppose that we
have another, even more preposterous, population B where all members mate
only with their first cousins. A and B start with a rare recessive
autosomal gene, heterozygotes (carriers) are 1 in 500 of the population.
In A, in the next generation, 1 in 1 million will be born homozygous
(1/500 X 1/500 X ¼). In B, the next generation will, to an approximation,
have 31 per million (1/500 X 1/64). Therefore, a family in B, involving
by definition a first-cousin marriage, has a 31-fold risk of having a
diseased child compared with a family in A. The excess of such children
in B over that in A is 30 per million.
But suppose A and B also start with a common recessive gene,
heterozygotes are 1 in 20 of the population. In A, in the next
generation, 625 per million will be born homozygous (1/20 X 1/20 X ¼). In
B, to an admittedly cruder approximation, neglecting several factors
without affecting the size of the effect too much, about 780 per million
will be born homozygous (1/20 X 1/64). This is only a 1.25-fold risk of
having an affected child for the first-cousin marriers of B compared with
the random maters of A, which seems at first to support Overall’s point.
However, comparing the populations, there is now an excess of well over
100 per million (780 – 625) of affected children in B. So on the
population, and on public health, the effect of first-cousin marriage on
common recessive genetic disorders has been even greater than the effect
on rare recessive genetic disorders.
Competing interests:
None declared
Competing interests: No competing interests
John Benson (BMJ, Dec 2005, p 1475), like many others, focuses
on consanguineous marriage as the cause of the relatively high
incidence of recessive disorders within the British Pakistani
population, and there is a very simple model to explain this
relationship: Recessive disorders require individuals to be
homozygous (having two copies) for the deleterious gene variant
and consanguinity increases the probability of offspring being
homozygous. However, although consanguinity is undoubtedly the
major contributor, population effects can also increase levels of
homozygosity and these too need to be considered.
In a recent genetic study of the Pakistani community of
Nottingham, we found that a high level of homozygosity was also
contributed to by population substructure, accounted for by the
presence of extended families, or biradheri (brotherhood).
Presumably, there has been limited inter-marriage between
biradheri, resulting in an uneven distribution of genetic variants,
and potentially a patchy distribution of recessive disease within the
community as a whole. The significance of biradheri in forming
endogamous kin-networks within which recessive variants may
drift into high frequencies therefore needs further attention.
Benson suggests that, until DNA diagnosis becomes a reality for
recessive conditions, non-consanguineous marriage may be the
only way to lower the risk of having affected children. This is only
true if the recessive variants are rare. For common variants
consanguineous marriage can have a negligible effect on the risk.
Consequently, the risks incurred by marrying non-
consanguineously (more distantly related than 2nd cousins) but
within the biradheri could still be high. Consanguinity can be
detrimental to health; understanding when this is the case would
allow health care workers to not only provide more informed
advice to potential parents, but hopefully offer advice less easily
dismissed than the recent high profile calls to stop consanguinity
(see Owen Dyer (BMJ, Dec 2005, p 1292)).
References
1/ Benson J. Recessive disorders and consanguineous marriage.
BMJ. 2005, 331: 1475.
2/ Modell B, Darr A. Genetic counselling and customary
consanguineous marriage. Nat.Rev.2002, 3: 225-229.
3/ Overall ADJ, Ahmad M, Thomas MG, Nichols RA. An analysis of
consanguinity and social structure within the UK Asian population
using microsatellite data. Ann. Hum. Genet. 2003, 67: 525-537.
4/ Dyer O. MP criticised for saying that marriage of first cousins is a
health problem. BMJ. 2003, 331: 1292.
Competing interests:
None declared
Competing interests: No competing interests
Owen Dyer (News, BMJ 3rd Dec 2005, p 1292) misquotes Alison Shaw.
The doubling of risk from 2 to 4% with cousin marriage is for all
congenital or genetic disorders, not recessive disorders, which are much
less common in the white population. In Blackburn we have found that our
Asian population has a 12 fold increased risk of recessive disorders
compared to the white population. In the Asian population there were 13
new recessive disorders per 1000 births. These figures are similar to a
number of other reports.
The burden of illness and handicap from these recessive disorders is
huge. Individual recessive disorders tend to cluster in family groups. The
simple message for the Asian community who favour cousin marriage is that,
if a recessive disorder is found in the family it is vital to seek genetic
advice before marrying and having children. In the majority of recessive
disorders in our Asian population a DNA diagnosis is still not possible.
This means that many families will need to consider non-consanguineous
marriage as the only way to lower the risk. For family groups in which
there is no known recessive disorder, cousin marriage will remain a
reasonable option.
References 1/ Kowariwalla S, Benson J. Recessive diseases in the
Blackburn Asian ethnic minority community; health
professionals’perceptions and families’response to genetic counselling.
2002. Unpublished.
2/ Modell B, Darr A. Genetic counselling and customary
consanguineous marriage. Nat.Rev.2002, 3: 225-229.
3/ Bundey S and Alam H (1993) A Five-Year Prospective Study of the
Health of Children in Different Ethnic Groups, with Particular Reference
to the Effect of Inbreeding. European Journal of Human Genetics 1: 206-
219.
Competing interests:
None declared
Competing interests: No competing interests
Re: MP is criticised for saying that marriage of first cousins is a health problem
The MP did of course stir up a hornets’ nest.
But nothing has happened.
Partly I must blame the use of euphemisms.
For example, the report in the Guardian, web edition, 15 Feb is headlined correctly - cousin marriages as a significant factor in child deaths. But, it goes on to talk of “South Asian practice”.
Cousin marriages are nothing to do with South Asia. Nor has it (as sometimes stated) anything to do with any religion.
According to Ullah, Hosseini, Mahmoud (1), consanguinous marriages are common in the rural and less educated populations in Pakistan. These authors also say that the practice is common in Saudi Arabia, Bahrain, Iran, Turkey.
By no stretch of imagination can one describe Saudi Arabia, Bahrain, Iran, Turkey as South Asian.
It seems reasonable to suggest that health education on the matter of recessive genes being more likely to come together in consanguineous unions should be given high priority. I would go further and suggest that first cousin marriages should be made illegal. A debate in the bmj would be welcome.
(1) International Jl of Community Medicine and Public Health. Ullah MA, Husseini AM, Mahmoud SU. 2018 Jan 5(1) 1-3
JK Anand
Competing interests: No competing interests