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Health

Cousin marriage should not be banned (?)

Gene ExpressionBy Razib KhanDecember 25, 2008 4:20 AM

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PLOS has a think piece up, "It's Ok, We're Not Cousins by Blood": The Cousin Marriage Controversy in Historical Perspective, which comes out against the laws in the United States which ban the marriage of cousins:

It is obviously illogical to condemn eugenics and at the same time favor laws that prevent cousins from marrying. But we do not aim to indict these laws on the grounds that they constitute eugenics. That would assume what needs to be proved - that all forms of eugenics are necessarily bad. In our view, cousin marriage laws should be judged on their merits. But from that standpoint as well, they seem ill-advised. These laws reflect once-prevailing prejudices about immigrants and the rural poor and oversimplified views of heredity, and they are inconsistent with our acceptance of reproductive behaviors that are much riskier to offspring. They should be repealed, not because their intent was eugenic, but because neither the scientific nor social assumptions that informed them are any longer defensible."

Here's a map which shows the time period when these laws were enacted:

cousinmap.jpg

Here are the numbers for the increased risk of congenital diseases for progeny of first cousin marriages:

Their report concluded that the risks of a first-cousin union were generally much smaller than assumed--about 1.7%-2% above the background risk for congenital defects and 4.4% for pre-reproductive mortality--and did not warrant any special preconception testing. In the authors' view, neither the stigma that attaches to such unions in North America nor the laws that bar them were scientifically well-grounded. When dealing with worried clients, the authors advised genetic counselors to "normalize" such unions by discussing their high frequency in some parts of the world and providing examples of prominent cousin couples, such as Charles Darwin and Emma Wedgwood....

These are obviously small elevated risks. When you move on to second or third cousins the genetic risks basically disappear. But, this is not the only issue. The authors note:

Third, as the report also notes, the degree of increased risk depends on the mean coefficient of inbreeding for the population. That is, whether first-cousin marriage is an occasional or regular occurrence in the study population matters, and it is thus inappropriate to extrapolate findings from largely outbred populations with occasional first-cousin marriages to populations with high coefficients of inbreeding and vice-versa. Standard calculations, such as the commonly cited 3% additional risk, examine a pedigree in which the ancestors (usually grandparents) are assumed to be unrelated. In North America, marriages between consanguineal kin are strongly discouraged. But such an assumption is unwarranted in the case of UK Pakistanis, who have emigrated from a country where such marriage is traditional and for whom it is estimated that roughly 55%-59% of marriages continue to be between first cousins...Thus, the usual risk estimates are misleading: data from the English West Midlands suggest that British Pakistanis account for only ~4.1% of births, but about 33% of the autosomal recessive metabolic errors recorded at birth...However, for a variety of reasons (including fear that a cousin marriage would result in their being blamed for any birth defects), UK Pakistanis are less likely to use prenatal testing and to terminate pregnancies...Thus the population attributable risk of genetic diseases at birth due to inbreeding may be skewed by prenatal elimination of affected fetuses in non-inbred populations. Moreover, the consequences of prolonged inbreeding are not always obvious. The uniting of deleterious recessives by inbreeding may also lead to these alleles being purged from the population. The frequency of such deleterious alleles, then, may be decreased, which (as shown above) means the relative risk is greater, even as the absolute risk decreases.

That's a mouthful. Here are the two main points: 1) Calculations of risk on the order of 2% may only be valid for cousin marriages in outbred populations. In societies where cousin marriage is preferred "cousins" may be related by numerous lines of descent, so their "real" relatedness is much greater than the norm for cousins. 2) This sort of extreme inbreeding can result in the purging of genetic load in the population because it "exposes" deleterious alleles to "selection." In other words, there is a light at the end of the tunnel whereby inbred populations may reduce their aggregate frequency of deleterious recessive alleles through the process of generating a higher than expected number of homozygotes than in a randomly breeding population. Consider a single gene deleterious recessive, if it is extant as a frequency of 10%, in a randomly breeding population only 1% of the population would manifest the deleterious phenotype. So only 10% of the deleterious alleles are subject to any selective pressure. If on the other hand there is a strong correlation in matings between those who carry the deleterious allele, then the proportion of those who express the phentoype increases, a larger proportion of the deleterious alleles are in individuals who have a homozygote recessive genotype. Finally:

Those who characterize it as slight usually describe the risk in absolute terms and compare it with other risks of the same or greater magnitude that are generally considered acceptable. Thus it is often noted that women over the age of 40 are not prevented from childbearing, nor is anyone suggesting they should be, despite an equivalent risk of birth defects. Indeed, the argument goes, we do not question the right of people with Huntington disease or other autosomal dominant disorders to have children, despite a 50% risk to offspring...On the other hand, those who portray the risk as large tend to describe it in relative terms. For example, geneticist Philip Reilly commented: "A 7 to 8% chance is 50% greater than a 5% chance. That's a significant difference." They also tend to compare the risk with others that are generally considered unacceptable. Thus a doctor asks (rhetorically): "Would anyone knowingly take a medication that has double the risk of causing permanent brain damage?"....

This is pretty understandable, there are many data which now suggest that older mothers and fathers are liable to produce children which have elevated health risks. And yet there are no laws against women and men over the age of 40 procreating. The authors point out possible sample bias in relation to prenatal testing and the disinclination among British Pakistanis to abort fetuses which carry deleterious recessive alleles in relation to the general population. This confound when comparing the rates of these diseases in terms of attributing them to consanguineous relationships can not be dismissed, but I think we shouldn't make too much of it, there's a reason that Saudi Arabia's health system is very primed to deal with progeny which manifest diseases common among those who are the products of consanguinity. The numerical value may shift once the confounds are removed, but the basic problem is real, and it will become more of an issue as generations of further inbreeding result in an increase in the number of homozygotes. In many of these societies though cousin marriages have been the ideal, only modern affluence and low mortality rates have allowed for the realization of these practices at their current rates. The rates of inbreeding are likely higher in much of the Muslim world today than in the past because of the proliferation of suitable relatives to marry, as well as more wealth which can be "kept in the family." One needs to differentiate between the relatively rare incidences of cousin marriage in a nearly panmictic population (e.g., United States), from societies where "cousin marriage" is far more frequent, on the order of 50% of marriages. I put cousin marriage in quotes because in those societies the coefficient of relatedness is going to be far higher than in normally outbreeding societies as individuals will marry within inbred clans. But, even in societies where cousin marriage is rare so that recessive diseases are less frequent, a 2% increased rate of these pathologies will have a non-trivial aggregate social cost. Consider a society where health insurance is a public good, paid out of the public purse from taxes levied upon all individuals. The choices of a pair of individuals are going to have an impact on the costs born by society as a whole. This is a general observation, not simply one limited to first cousins. There is a clear analogy to older mothers, and lesser extent, fathers, illustrates the general point. I've talked about Down Syndrome and abortion rates in the past. Private choice and public obligations are interrelated in human societies, and decisions are often made in the context of what is socially acceptable. Consider two individuals who are carriers of Cystic Fibrosis, there is almost certainly going to be some social disapproval if these individuals wish to have a family and reject selective abortion or pre-implanation screening on principle. The case of Cystic Fibrosis brings me to the argument about inbreeding purging genetic load. To me, it elicits the observation in that in the long run we're all dead. European populations could "purge" the Cystic Fibrosis allele from the population by proactively bringing together those who carry the allele so that a higher proportion of individuals within the population who carry the allele have it "exposed" to "selection." By exposed to selection I mean that individuals will be born with Cystic Fibrosis, and due to their illness have sharply reduced fitness. So let me just say this: the argument that inbreeding will purge genetic load is true in theory but crazy in practice! It may be true, but who the hell really wants to Ashkenazi Jews who carry Tay-Sachs to marry so that the allele can be "exposed"!?!?! Pointing out the salubrious long-term impact of inbreeding is not only crazy, but it ignores the possibility of pedigree collapse leading to mutational meltdown. It's happening today to the Samaritans; generations of inbreeding have not produced superior individuals purged of deleterious alleles, rather, it has generated a population on the verge of biological extinction because of high rates of birth defects. Population genetics can tell us a lot about inbreeding as biological phenomenon, but at the end of the day this is also social and ethical issue. It can be argued that societieswherecousinmarriage is the norm are not favorable for the generation of dispersed social capital and trust necessary to produce civil society which aids in the perpetuation of liberal democracy. The Catholic Church's medieval campaign against cousin marriage was not at the root based on a genetic rationale, rather, it was likely due to the fact that banning marriage between cousins to many degrees of relation sharply reduced the local mating pool for elites. Not only would this prevent the emergence of incestuous clans which would rival the Church as loci of power, but it also meant that individuals who did not marry and reproduce would likely leave their estates to the Church (this is one reason there was a campaign against adoption as well).^1 The Protestant Reformation saw an immediate increase in the rate of cousin marriage across Northern Europe among elites; obviously the power of the Church had constrained a practice for which there was a demand. With the reduction in family size (shrinking the pool of partners), modern transportation and a more dynamic economy not based on rent-seeking, the older rationales for cousin marriage have mostly faded in the developed world. Implicit in my piece for Comment Is Free in The Guardian is that marriage, or relationships in general, should be viewed as more than simply a legal transaction defined by negative liberty. The arguments about gay marriage in the United States illustrate both the positive and negative arguments; on the one hand many contend that legal recognition is critical to their worth in the eyes of society, while others suggest that gay marriage is simply an application of the same treatment which others receive. I believe that the former one should be taken to heart more, whether one agrees with it or not, because relationships are more than transactions between consenting adults, they are critical cement which bind cultures and societies. Polygamous relationships where males have multiple wives are not historically uncommon, and in most cultures they have been the idealized norm. They are most certainly not "against nature," and many religions have sanctioned this practice. The reason that the Malaysian prime minister argued against the practice, which is recognized by the established religion, has to do with a particular positive conception of what women should expect from a man within a marriage, and the consequences of males who have progeny in several parallel families. This non-individualistic take, a utilitarianism within a particular values framework, can be generalized. Within regards to marriage of cousins, or women having children in their 40s and men fathering children in their 60s, there are consequences in the lives of these children and on society as a whole, which emerge from these acts which are not simply ones of increased risk of biological pathology. Even within the domain of medicine procreation is more than the result of an act between two consenting adults. It seems likely that within the next 10 years the United States will take the plunge and accept that a substantial portion of the public purse will be devoted to the health care of all Americans (Medicaid and Medicare mean that the system is already partly socialized). If we are our brother's keeper, then their business starts to become our business. Lines will be drawn on what is acceptable, and what is not, as they always have been. The plurality of ethical systems which we accept as normal will run up against the fact that the unitary state will collect taxes from everyone to fund a finite set of actions which may not comport with the ethical systems of many (the debates over government funding of abortion in the military is just a taste of what is likely to come). The biological rationales for, or against, cousin marriage may or may not be persuasive, but they exist embedded within a much bigger picture which strikes to the root of ancient ethical conundrums as to how to perpetuate the "Good Life."Related: There's a biological argument cousins marrying too. Here's a global map of consanguineous relationships:

Globalcolorsmall.jpg

Here's a Google Maps interface from Consang.net. 1 - In the pre-modern period the Church's interference in marriage was mostly something that only applied to elites. Additionally, the Church also looked the other way on many occasions, and the rules in regards to incest were so strong (e.g., out to 7 degrees) that it was a back-door which one could use to annul marriages.

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