The imbalance of 513 to 449 for schizophrenia amounts to a 53:47 split per hundred SNPs. The table of 22 traits related to cognitive repertoires presented above has a total of 66 cross-continent pairs. The imbalance is at least 53:47 for 48 of those 66 pairs. It is 55:45 or greater for 33 of them. It is 60:40 or greater for 8 of them. No matter what (reasonable) criterion for a large-enough imbalance you might adopt, many imbalances qualify as large enough to warrant investigation. In time, they will in fact be investigated. It is implausible to expect that none of the imbalances will yield evidence of significant genetic differences related to phenotypic differences across continental populations.
The results will often be complex. The same SNPs that affect the trait under investigation will typically be correlated with many other traits as well, which may sometimes mean that SNPs beneficial for a desirable trait also increase vulnerability to undesirable ones, as in the case of the tradeoff between protection against malaria versus the risk of sickle cell anemia. Some analyses may reveal that different populations get to similar end points via different processes, as in the case of sex differences in cognitive toolboxes discussed in chapter 3. But simple or complex, the results are in my view bound to be interesting.
Whether my forecast is reasonable depends on the outcome of a larger debate about establishing genetic causation. One side of that debate holds that my optimism is dead wrong. The results cannot possibly be interesting, because causation cannot possibly be established even after the problems of population stratification have been solved. That debate is given a full discussion in chapter 14. It seems fair to say at least this: It is fundamentally wrong to think of the study of genetic population differences as an exercise in ranking populations from top to bottom. The questions to be explored are far more interesting, complex, and potentially more rewarding than filling out an ethnic scorecard.
WHAT ABOUT UNCOMMON AND RARE VARIANTS?
Most single nucleotide variants (SNVs) are found in fewer than 1 percent of chromosomes and therefore do not qualify as common SNPs. The proportion of SNVs with allele frequencies of less than .01 is currently estimated at 74 percent, but that’s going to increase as more rare variants are discovered.17 The closest to a complete inventory as I write is a 2016 sample based on 10,545 genomes that used deep sequencing techniques and identified 150 million variants in the human genome. This is by no means the total. The study reported that each individual added to the sample contributed 8,579 variants not previously identified, leading the authors to estimate that a sample of 100,000 genomes would identify 500 million variants.18 How much additional variance rare variants explain is still uncertain—a few articles have reported that they explain much of the missing heritability in GWAS analysis, but most analyses show minor effects.19
In addition to constituting the bulk of all variants, rare variants are also overwhelmingly confined to a single continental population, on the order of 90 percent or more.20 However, the importance of rare variants to population differences is uncertain. By one line of argument, they should be minor. By definition, a rare SNV has not spread widely through a population. It is either a new mutation or one that has been only weakly selected if at all. Mutations are random events. They don’t happen because there’s a need for them (e.g., a mutation giving protection against a disease does not occur because the person was living where the disease was endemic). Thus there is no reason to believe that new mutations occurring in two separated populations will be systematically different with regard to their effects on a given trait. But the literature contains a variety of other perspectives on the role of rare variants.[21] The short story is that comparatively little is known about the role of rare variants, both generally and with regard to population differences. The action for now is with standing variation in common SNPs.
Known Genetic Continental Population Differences
Our expectations for the future should take into account that many genetic population differences are already established.
Hiding in Plain Sight
We have known for years that biologically complex differences in continental populations have evolved since humans left Africa. It is an unlikely assertion on its face—how can “race is a social construct” continue to be the received elite wisdom if such differences are already known? But it’s true. Two examples of significant genetic differences across populations have been sitting in plain sight for decades: lactase persistence and susceptibility to sickle cell anemia. Details on both of these adaptations are given in the note.[22] Both of these are major adaptations involving many biological systems. For that matter, lightening of skin pigmentation, passed off as trivial because it is only “skin deep,” is genetically more complicated than “skin deep” implies.[23] Why, given these examples of complex adaptation that obviously occurred after the Africa exodus, should it ever have been assumed that they were the only ones?
Continental Differences Discovered Through Genome-Wide Analysis
Even though the documentation of continental differences has had a low priority among most genetics researchers, several have been found.
Susceptibility to inflammatory and immune-related diseases. In 2014, Jessica Brinkworth and Luis Barreiro examined the GWA results for three chronic inflammatory diseases (celiac disease, Crohn’s disease, and ulcerative colitis) and five autoimmune diseases (type 1 diabetes, multiple sclerosis, rheumatoid arthritis, psoriasis, and systemic lupus erythematosus). They found evidence “that at least some of the present-day autoimmune risk loci have been adaptive and conferred some sort of functional benefit to Europeans in the past.”24 The authors hypothesized that a large sample of Africans would yield evidence that “the genetic determinants of susceptibility to chronic inflammatory and autoimmune diseases in individuals of African descent are distinct from those found among Europeans.”25 A 2016 study conducted by a large international team (first author was Yohann Nédélec) found evidence that differences in immune function arose from natural selection rather than genetic drift: “More specifically,” the authors wrote, “our results suggest that a significant fraction of population differences in transcriptional responses to infection are a direct consequence of local adaptation driven by regulatory variants.”26
A study of psoriasis using samples of Europeans (called Caucasians in the study) and Chinese identified European-specific loci that had a cumulative effect that “could explain up to 82.83 percent of the prevalence difference of psoriasis between the Caucasian and the Chinese populations.”27 Overall, the authors concluded, “This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.”28
Respiratory adaptation to high altitudes. Adaptation to high altitudes has occurred among peoples living on the Qinghai Plateau in Tibet, the Andean Altiplano in Peru, and the Semien Plateau in Ethiopia involving changes in pulmonary function, arterial oxygen saturation, hemoglobin concentration, and maternal physiology during pregnancy. The evolutionary routes taken by each population have involved different genes and produced different responses.29 Resting ventilation among the Andeans is normal for humans in general; among Tibetans, it is 50 percent higher. Arterial oxygen saturation is elevated for Andeans and Ethiopians; not for Tibetans. Hemoglobin concentration is elevated among Andeans, shows a minimal increase among Ethiopians, and is actually lowered in Tibetans.30 An exotic complication in the case of the Tibetans is that some of the mutations that helped adapt them to high altitude now appear to have come from introgression with the mysterious Denisovans.31
Genetic disorders among Ashkenazi Jews. As early as the 1880s, it was noted that Tay-Sachs disease occurred almost exclusively among Ashkenazi Jews. Over the years, several other genetic disorders have been found to be far more prevalent among Ashkenazi Jews than in any other population. The causes of the difference in prevalence are still unresolved. On
e possibility is a population bottleneck around a thousand years ago, as argued in a 2018 study that analyzed 5,685 Ashkenazi Jewish exomes. The alleles in question included ones for Tay-Sachs.32
Another possibility is that natural selection has been at work. In 2009, before access to GWA, Gregory Cochran and Henry Harpending argued that case, observing that the Jewish genetic disorders are oddly grouped:
Imagine a fat biochemistry textbook, where each page describes a different function or condition in human biochemistry. Most of the Ashkenazi diseases would be described on just two of those pages. The two most important genetic disease clusters among the Ashkenazim are the sphingoloid storage disorders (Tay-Sachs disease; Goucher’s disease; Niemann-Pick disease; and mucolipidosis, type IV) and the disorders of DNA repair (BRCA1 and BRCA2; Fanconi anemia, type C; and Bloom syndrome).33
If a population bottleneck were the sole explanation, they calculated that the odds of finding four disorders that affect sphingolipid metabolism would have been about 1 in 100,000.[34] The authors concluded instead that we are looking at recently evolved differences across populations. While the explanation remains unclear, this much is undisputed: The disorders are genetic, and so are population differences separating Ashkenazi Jews from everyone else.
Prostate cancer. In 2018, a team of geneticists (first author was Joseph Lachance) studied the genetic sources of the differential rates of prostate cancer in Europeans and Africans. They used SNPs from the GWAS Catalog, Phase 3 of 1000 Genomes, and the large database of African genomes assembled by Sarah Tishkoff of the University of Pennsylvania. They found that a small proportion of SNPs with large target allele frequency differences and large effect sizes make a disproportionate contribution to population differences in the risk of prostate cancer. “Both neutral and selective evolutionary mechanisms appear to have contributed to disparities in the genetic risk of CaP. These mechanisms include founder effects due to the out-of-Africa migration and genetic hitchhiking of disease susceptibility alleles with locally adaptive alleles.”35
Evidence of natural selection in height, schizophrenia, and body mass index. A team of geneticists (first author was Jing Guo) examined height, body mass index, waist-hip ratio adjusted for BMI, HDL cholesterol, LDL cholesterol, coronary artery disease, type 2 diabetes, Alzheimer’s disease, schizophrenia, and educational attainment for evidence of natural selection. The Guo study tapped a variety of databases instead of limiting itself to the GWAS Catalog. The authors found evidence that SNPs associated with height, schizophrenia, and waist-to-hip ratio have undergone natural selection.36 They did not find such evidence for the other seven traits in the study.
Blood pressure. A study by a team of Japanese geneticists (first author was Fumihiko Takeuchi) used Europeans and East Asian samples to study continental population differences in blood pressure. They found evidence for two remarkable phenomena: “(1) the colocalization of distinct ancestry-specific variants that are not rare and can exert mutually inverted genetic effects between the ethnic groups and (2) the potential involvement of natural selection in the occurrence of ancestry-specific association signals.”37 They argued that “we have discovered a new model in which genetic effects for transethnic SNPs that form a shared haplotype at a locus are driven by causal variants that are ancestry-specific but are not rare, which can be called a common ancestry-specific variant association model.”38
And more. Greenlandic Inuits are genetically adapted to a marine diet rich in omega-3 polyunsaturated fatty acids, increasing fitness in a cold and dark environment.39 The population of San Antonio de los Cobres in Argentina has adapted to high levels of arsenic in the groundwater through positive selection on SNPs involved in the arsenic methylation pathway.40
It’s early days yet, but the results of the limited genome-wide analyses of differences in continental populations to date point in the same direction: Many continental population differences are out there.
Recapitulation
The story of the raw material for studying continental population differences applies to SNPs related to physiological parameters, diseases, and cognitive repertoires. Substantial between-continent differences in target allele frequencies are common. Around a third of all differences meet a plausible definition of “large.” The limited amount of sophisticated genetic analysis of between-continent differences done to date suggests that these extensive differences observed in the raw material will frequently yield productive results about genuine continental population differences.
A Personal Interpretation of the Material in Part II
Part II has described a parallel universe. In the universe inhabited by the elite media and orthodox academia, it has been settled for decades that race is a social construct. In that universe, the lessons taught by Richard Lewontin and Stephen Jay Gould back in the 1970s and early 1980s still apply.
In the universe inhabited by geneticists who study human populations, the 1990s saw glimpses of a new perspective, and the new century opened up fascinating stories that had previously been closed.
The new understandings about the peopling of the Earth have been the most dramatic. New roles in the evolution of Homo sapiens were discovered for Neanderthals and previously unknown hominins. Access to ancient DNA enabled the reconstruction of successive human migrations across Eurasia that have revolutionized our knowledge of prehistory.
The understanding of recent evolution that prevailed as recently as the 1990s has also been overturned. Human evolution does not always proceed at a glacial pace dictated by random mutations. Sometimes changes in standing variation can occur quickly in response to environmental selection pressures. Those environmental pressures have typically been confined to populations in specific geographic areas.
Most recently, the task of assembling the genetic story for specific phenotypic traits has begun. It is still in its early stages, but progress is accelerating nonlinearly. Hence the nervousness that has prevented open discussion of what’s going on in the geneticists’ parallel universe: the fear that we will discover scary population differences in what I have called cognitive repertoires.
That fear accounts for the taboo that has been attached to discussions of genetics and race. It’s no wonder. White Americans’ justified guilt about their history of discrimination against blacks, native Americans, and immigrants from Latin America and East Asia gives them reason to worry that white supremacists will use genetics to rationalize that history.
Let me suggest an alternative way of thinking about ethnic differences. Many of the people in elite circles who honor the taboo are also cosmopolitan. They have had professional colleagues of many ethnicities and have traveled extensively, observing the endless variety of ways in which people in different cultures think and behave. They have no trouble believing from personal experience that Chinese think and behave somewhat differently from Saudi Arabians. So do Saudi Arabians and Senegalese, Senegalese and Norwegians, Norwegians and Italians, northern Italians and southern Italians. Viewed from that perspective, ethnic differences in cognitive repertoires are neither to be doubted nor feared. They exist, and everyone who has seen anything of the world knows it. The mix of nature and nurture? That’s not the issue. The differences themselves are facts. People around the world are similar in the basics and different in the details. We connect through the basics. We live with and often enjoy the differences.
The material in Part II does not foreshadow discovery of genetically-grounded population differences in the basics. Rather, I hope I have persuaded you that genetically-grounded differences in the details are to be expected. Some of these genetic differences may consist of alternative routes for getting to similar ends, just as has been found with many cognitive sex differences. Many others will be differences that are neither better nor worse, but just differences. Probably some will lend themselves to value judgments, but even those will cut both ways. No population is free of defects nor possessed of all the virtues.
We can expect most of the genet
ic differences to range from small to moderate and to explain just a portion of the phenotypic differences we already live with. Every population will be represented from one extreme to the other on every trait. There will be no moral or legal justification for treating individuals differently because of the population to which they belong.
I doubt that these assurances will do much good. The prospect of genetic differences across ancestral populations is still too sensitive for calm discussion. But perhaps this will provide perspective:
We already know of a genetically-grounded population difference on a highly sensitive trait that is far, far larger than any ancestral population difference we are going to find. The populations in question are males and females. The highly sensitive trait is the commission of physical violence against other humans. The undoubted genetic source of the difference is the Y chromosome. How big is the difference? Judge it by this: About 90 percent of all homicides are committed by males.41
If we can live with a population difference that huge on such an important behavioral trait, we can easily live with the smaller differences in continental populations that are likely to be found. The differences that will be documented during the coming years should be greeted with “That’s interesting.” I fear that the orthodoxy’s insistence that population differences in cognitive repertoires cannot exist ensures that they initially won’t be greeted that way.[42] But they should be.
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