Natural History of Ashkenazi Intelligence

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There are a number of genetic diseases that are unusually common among the Ashkenazim. We also know a fair amount about genetic disease among the Sephardic and Asian Jews: How can we categorize these diseases and the associated mutations?

Most fall into a few categories, as noted by Ostrer: sphingolipid storage diseases, glycogen storage diseases, clotting disorders, disorders of adrenal steroid biosynthesis, and disorders of DNA repair. It is interesting that although several Jewish disorders fall into each of these categories, sometimes several in the same population, none of the Finnish genetic diseases, for example, fall into any of these categories (Norio), while only one of the genetic disorders common in Quebec does, Tay-Sachs (Scriver). But that is as expected: genetic diseases made common by drift would be very unlikely to cluster in only a few metabolic paths, as if on a few pages of a biochemistry text. The existence of these categories or disease clusters among the Jews suggests selective forces at work, just as the many different genetic disorders affecting hemoglobin and the red cell in the Old World tropics suggest selection, which we know is for malaria resistance.

The two most important genetic disease clusters among the Ashkenazim are the sphingolipid storage disorders (Tay-Sachs, Gaucher, Niemann-Pick, and mucolipidosis type IV) and the disorders of DNA repair (BRCA1, BRCA2, Fanconi’s anemia type C, and Bloom syndrome) but there are several others that are at quite elevated frequency in Ashkenazim. Using published allele frequencies we can calculate that the probability at conception of having at least one allele of the sphingolipid or DNA repair complex is 15%. If we add Canavan disease, familial dysautonomia, Factor XI deficiency (Peretz et al.), and the I1307K allele of the APC locus (Gryfe et al.) this figure grows to 32%, and if we further include non-classical congenital adrenal hyperplasia the probability of having at least one allele from these disorders is 59%.

The sphingolipid storage mutations were probably favored and became common because of natural selection, yet we don’t see them in adjacent populations. We suggest that this is because the social niche favoring intelligence was key, rather than geographic location. It is unlikely that these mutations led to disease resistance in heterozygotes for two reasons. First, there is no real evidence for any disease resistance in heterozygotes (claims of TB resistance are unsupported) and most of the candidate serious diseases (smallpox, TB, bubonic plague, diarrheal diseases) affected the neighboring populations, that is people living literally across the street, as well as the Ashkenazim. Second and most important, the sphingolipid mutations look like IQ boosters. The key datum is the effect of increased levels of the storage compounds. Glucosylceramide, the Gaucher storage compound, promotes axonal growth and branching (Schwartz et al.). In vitro, decreased glucosylceramide results in stunted neurons with short axons while an increase over normal levels (caused by chemically inhibiting glucocerebrosidase) increases axon length and branching. There is a similar effect in Tay-Sachs decreased levels of GM2 ganglioside inhibit dendrite growth, while an increase over normal levels causes a marked increase in dendritogenesis. This increased dendritogenesis also occurs in Niemann-Pick type A cells, and in animal models of Tay- Sachs and Niemann-Pick.

Dendritogenesis appears to be a necessary step in learning. Associative learning in mice significantly increases hippocampal dendritic spine density, while enriched environments are also known to increase dendrite density. It is likely that a tendency to increased dendritogenesis (in Tay-Sachs and Niemann-Pick heterozygotes) or to increased axonal growth and branching (in Gaucher heterozygotes) facilitates learning. Heterozygotes have half the normal amount of the lysosomal hydrolases and should show modest elevations of the sphingolipid storage compounds. A prediction is that Gaucher, Tay-Sachs, and Niemann-Pick heterozygotes will have higher tested IQ than control groups, probably on the order of 5 points.

 

Natural History of Ashkenazi Intelligence

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