Genome-wide autozygosity is associated with lower general cognitive ability

[Angela]

Genome-wide autozygosity is associated with lower general cognitive ability

This is the link to the article:
http://www.nature.com/mp/journal/vao...p2015120a.html

I can't access the entire article, but this is the abstract:

"Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity—multiple homozygous SNPs in a row—to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P=0.003–0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time."

My take-away: Generally speaking, first cousin marriages are a really bad idea.

The only caveat might be that if the founding population was one that had already selected for high cognitive skills (Brahmins who as priests had to be literate, for example) then this might not happen. Of course, they suffer disproportionately from certain diseases, as well.

[RobertColumbia]

...The only caveat might be that if the founding population was one that had already selected for high cognitive skills (Brahmins who as priests had to be literate, for example) then this might not happen. Of course, they suffer disproportionately from certain diseases, as well.

That's a good point. I have heard speculation that the apparent increase in autism may be partially fueled by marriages between highly literate people. Some research (citation within) indicates that a high intelligence can also mean high susceptibility to some mental health issues.

[Angela]

That's a good point. I have heard speculation that the apparent increase in autism may be partially fueled by marriages between highly literate people. Some research (citation within) indicates that a high intelligence can also mean high susceptibility to some mental health issues.

That correlation between high verbal IQ and anxiety/depression (which are often co-morbidities) totally makes sense to me. The better your memory for conversations etc., the more you can "replay" certain painful moments in your life, and the more analytical you are, the more you can tend to, as the article says, think of every possible outcome or consequence of certain situations, including negative ones. I think other things like innate optimism versus pessimism, and even learned pessimism have their part to play, though.

The only antidote is to put them out of your mind as much as possible. Those negative things might not happen. If they do you'll suffer then. Why suffer twice? :)

I think a lot of other kinds of mental illness don't necessarily correlate with intelligence. Prisons are full of very low IQ people many if not most of whom are either bipolar or schizophrenic.

[Tomenable]

increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins

That's a drop of around 10 IQ points (1 s.d. = 15 points, IIRC) - so quite a lot.

Unsurprisingly many people from countries with high rates of marriages between close relatives don't shine on IQ tests:

Figures from October 2009 (white colour = no data):

[Angela]

They're talking about marriages between first cousins. Every study I've read on the subject, including the mammoth one by Cavalli-Sforza, shows that by the time you get to third cousins there's no effect at all, so the charts are not exactly on point.

Regardless, as we were discussing, a lot depends on the alleles present in the group to begin with...i.e. Brahmins.

Ed. Or the Ashkenazim, for that matter. Even uncle/niece marriage is still permitted among the Orthodox. I think I read somewhere that the Rothschilds have a history of first cousin marriages and even uncle/niece ones until the last hundred years or so. It certainly didn't seem to affect their IQ.

On the other hand, look at the royal families of Europe. Where would they fall in society if it weren't for their inherited positions? I think I read that some English Duke whose family money ran out is working as a gardener. Now that they have to meet the regular requirements the royals certainly aren't getting into Oxford and Cambridge anymore.

[Finalise]

Well, with first cousins you share 2 out of 4 grandparents. That's 50% of your genes. It's like having a relationship with a half-sibling. With a second cousin, you share 2/8 great-grandparents, and the damage is mitigated.

[LeBrok]

I wonder how hunter gatherers in small groups, like in Amazon jungle these days, or many groups of hominids in the past, for thousands upon thousands of years, could survive with so much inbreeding? I shouldn't even mention Adam and Eve story.

[Finalise]

They had the life expectancy of a horse

[LeBrok]

They had the life expectancy of a horse

Yes, without soup, good hygiene, antibiotics, plentiful food, hospitals, but lived with tape worms, hook worms, pin worms, flees, lice, etc. Take away modern technology and you will see how short we will live.

[Angela]

I wonder how hunter gatherers in small groups, like in Amazon jungle these days, or many groups of hominids in the past, for thousands upon thousands of years, could survive with so much inbreeding? I shouldn't even mention Adam and Eve story.

I think they barely survived, yes? Didn't the paper on Loschbour state that he carried a large "genetic load" or package of deleterious mutations?

The same was true in the Neanderthal and Denisovan groups, I think.

[epoch]

I think they barely survived, yes? Didn't the paper on Loschbour state that he carried a large "genetic load" or package of deleterious mutations?

The same was true in the Neanderthal and Denisovan groups, I think.

Our best proxy for the paleolithic are traditional aboriginals. They had a rather complicated set of taboos regarding who to marry. It resulted in marriage outside the local group but inside the extended group.

http://guurrbitours.blogspot.nl/2011...ge-taboos.html

As children take the moiety of their birth father, I had to choose a marriage partner from my mother's side of the family - but not 'too close' and preferably from a distant geographic area.

There is also some evidence of patrilocality in Neandertals which at least may indicate marrying wives from outside the local group.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088635/

The claim of patrilocality rests on the observation that three adult males all have the same mtDNA haplotype, whereas three adult females each carry a different mtDNA lineage. The observation of higher female than male mtDNA diversity within a group is not an indication of patrilocality, however, because males simply carry the mtDNAs of their mothers. If the females in the studied group had each survived and reproduced, their male offspring would have borne three different lineages, and thus appear quite diverse compared with the males in the parental generation or females of their own generation.

[LeBrok]

Our best proxy for the paleolithic are traditional aboriginals. They had a rather complicated set of taboos regarding who to marry. It resulted in marriage outside the local group but inside the extended group.

http://guurrbitours.blogspot.nl/2011...ge-taboos.html



There is also some evidence of patrilocality in Neandertals which at least may indicate marrying wives from outside the local group.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088635/

Such traditions and practices can explain why mtDNA is rather evenly distributed through Europe without explanation relying only on rapes, wars and stealing women.

[Angela]

Isn't the best evidence for inbreeding among ancient humans the genomes of those ancient humans? http://www.huffingtonpost.com/2013/1...n_4472387.html

"We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors." http://www.nature.com/nature/journal...ture12886.html

Low genetic diversity may have led to their extinction. http://www.pressherald.com/2013/12/1...l_inbreeding_/

As to Loschbour, he was apparently not recently inbred, but his genome shows a very strong bottleneck in his ancestors, according to Lazaridis et al. (Extended Data Figure 2)

This ties in with this article based on an interview with Pinhasi. It will be interesting to read the papers that come out of the research: http://horizon-magazine.eu/article/i...nction_en.html

"This demographic model is based on new evidence that suggests populations were much smaller than is generally thought to be a stable size for healthy reproduction, usually around 500 people. Such small groupings may have led to reduced fitness and even extinctions. ‘

As an archaeologist and anthropologist, I was quite shocked to see how limited, how small the population numbers were. You know, shockingly small,’ said Prof. Pinhasi, based at University College Dublin, Ireland. ‘I think that what happened, it’s on a catastrophic level of demography for a long time in human evolution,’ he said."

The same issue is addressed in the following paper: http://www.sciencedirect.com/science...69534713002322

"For mutations on which natural selection can act (i.e., those with s != 0, Box 2), the NeRR depends on the fitness effects of mutations (s, Figure 1). As Ne increases, natural selection becomes more effective at fixing advantageous mutations and removing deleterious mutations, but larger populations also produce more of both types of mutation. Theory sug- gests that as Ne increases the power of natural selectionincreases faster than the production of new mutations (see [5] for a recent review). This results in lower deleterious substitution rates as Ne increases (a negative NeRR,Figure 1B,D), and higher advantageous substitution ratesas Ne increases (a positive NeRR, Figure 1A,C).

As to genetic fitness in Loschbour: "In conclusion, these results point to either a less effective removal of lightly deleterious mutations in Loschbour or a population bottleneckin Loschbour history,which would increase the relative fraction of deleterious mutations in protein-coding regions. In either case, the observation points to a history of smaller population size in Loschbour than in Stuttgart and present-day humans since their separation."

La Brana was a similar case.

See also this review of " Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes" by Razib Khan: http://www.unz.com/gnxp/genetic-load...ide-of-africa/

" the power of selection to remove deleterious mutations is hampered the smaller the effective population size, as random genetic drift becomes more determinative in generation to generation changes in allele frequency."

The power to fix advantageous mutations is also smaller with smaller effective population size.

I think it's clear that there's a distinction between close recent inbreeding, which was the topic of the conversation, and bottlenecks and low effective population size. Both have deleterious consequences.

[Tomenable]

They're talking about marriages between first cousins. Every study I've read on the subject, including the mammoth one by Cavalli-Sforza, shows that by the time you get to third cousins there's no effect at all, so the charts are not exactly on point.

The charts I posted show only first and second cousins. Marriages between third cousins are not even considered consanguineous.

In Pakistan 70% of marriages are between first or second cousins (or sometimes even siblings), in Iraq about half of marriages.

Muslim Sunnah praises and encourages marriages between close relatives. Already Muhammad himself married his first cousin.

I think I read somewhere that the Rothschilds have a history of first cousin marriages and even uncle/niece ones until the last hundred years or so. It certainly didn't seem to affect their IQ.

It is gambling. The Habsburgs also had a history of inbreeding and some branches of the dynasty did fine, but most ended badly.

Maybe it did not affect Rotschild IQ but it could affect other mental traits among them. Sociopathy for example is largely genetic.

[Tomenable]

As for evidence for inbreeding among ancient humans:

Here is evidence that Europeans during the so-called "Dark Ages" - in this case Anglo-Saxons - were often inbred:

Out of 3 Anglo-Saxons buried at Hinxton, 3 were inbred:

http://www.fi.id.au/2014/10/how-hinx...ach-other.html

Based on Runs of Homozygosity, we know the following.

Hinxton-2 parents are first cousins.
Hinxton-3 parents are first or second cousins.
Hinxton-5 parents are half siblings.

Hinxton-2 and Hinxton-3 were from 1st/2nd cousin marriages, but Hinxton-5 was even a child of half siblings.

[Regio X]

Well, with first cousins you share 2 out of 4 grandparents. That's 50% of your genes. It's like having a relationship with a half-sibling. With a second cousin, you share 2/8 great-grandparents, and the damage is mitigated.

We share 50% of our genes with each parent and almost the same with our siblings (not 100%, of course), about 25% with a half-sibling and about 12.5 with a first cousin.

http://dna-explained.com/2012/08/19/...ts-the-basics/ (go to "Relationship Predictions")

% of DNA shared: http://dna-explained.com/2013/09/29/...tch-my-cousin/

How many genetic ancestors do I have? http://gcbias.org/2013/11/11/how-doe...ack-over-time/

How much of your genome do you inherit from a particular ancestor? http://gcbias.org/2013/11/04/how-muc...ular-ancestor/

[Angela]

The charts I posted show only first and second cousins. Marriages between third cousins are not even considered consanguineous.

In Pakistan 70% of marriages are between first or second cousins (or sometimes even siblings), in Iraq about half of marriages.

Muslim Sunnah praises and encourages marriages between close relatives. Already Muhammad himself married his first cousin.



It is gambling. The Habsburgs also had a history of inbreeding and some branches of the dynasty did fine, but most ended badly.

Maybe it did not affect Rotschild IQ but it could affect other mental traits among them. Sociopathy for example is largely genetic.

I hadn't heard that the Rothschilds were famous for the number of sociopaths among them. I've only ever known of them from their philanthropic endeavors and participation in the arts world, in addition to their wealth, of course. Unless having a great financial mind and making tons of money makes you a sociopath.

You're right, in my opinion: first cousin marriages, especially repeated first cousin marriages, are a gamble. Generally it's not a good idea. The Hapsburgs are indeed a prime example.

https://en.wikipedia.org/wiki/Carlos...ce_of_Asturias

As the article explains:
"Carlos had only four great-grandparents instead of the maximum of eight,^[2] and his parents had the same coefficient of coancestry (1/8) as if they were half siblings. He had only six great-great-grandparents, instead of the maximum 16;^[2] his maternal grandmother and his paternal grandfather were siblings, his maternal grandfather and his paternal grandmother were also siblings, and his two great-grandmothers were sisters."

Yikes! It's amazing that they kept this up generation after generation. Why did they think the Church had all those rules about needing dispensations for marriages closer than third cousins? Somebody at some point had figured it out.

[epoch]

Such traditions and practices can explain why mtDNA is rather evenly distributed through Europe without explanation relying only on rapes, wars and stealing women.

Especially during the Middle Ages as the church forbade cousin marriages a mixture of endogamy and exogamy would exist. It most probably also would even out autosomical differences. [1] However rape, war and stealing women existed among the aforementioned Aboriginals as well and there is a plethora of evidence it existed in the neolithic as well as in the periods before that. The Motala skull were stuck on poles, for example.

[1] Mind you, if you take a look at several of the recently published late neolithic genomes you see they differ from present-day Europeans, even if far less than older examples. They also differ from each other. I often wonder how much of that is due to the fact that once researchers want to retrieve the genome of a certain culture they will try to find remains from sites that a very typical for those cultures. But that introduces the bias that you may select for pure, new settlements rather than mixed ones.