Sunday, October 21, 2018

The Truth Shall Make You Free

Note Added in response to 2020 Twitter mob attack which attempts to misrepresent my views: This is not my research. I do not work on population structure or group differences in genomics. I also do not work on signals for recent natural selection. The post below discusses whether researchers should be forced to abandon important lines of investigation because of moral panics caused by misunderstanding of their results. What I told NYT reporter Amy Harmon at the time: These are serious, well-meaning researchers. You can't sensationalize their work and then force them to make loyalty pledges.

Racist inferences based on the results are the fault of the reader, not the authors of the papers or of this blog.

These NYTimes articles by Pulitzer Prize winner Amy Harmon, linking genetic science to racism and white supremacy, caused a sensation at ASHG 2018, a large annual meeting of genetics researchers.
Why White Supremacists Are Chugging Milk (and Why Geneticists Are Alarmed)

‘Could Somebody Please Debunk This?’: Writing About Science When Even the Scientists Are Nervous

Geneticists Criticize Use of Science by White Nationalists to Justify ‘Racial Purity’
In the second article above, Harmon writes
But another reason some scientists avoid engaging on this topic, I came to understand, was that they do not have definitive answers about whether there are average differences in biological traits across populations. And they have increasingly powerful tools to try to detect how natural selection may have acted differently on the genes that contribute to assorted traits in various populations.

What’s more, some believe substantial differences will be found. ...
The first talk I attended at ASHG this year is summarized below. The talk was oversubscribed, so I had to sit in the overflow room. One of the slides presented showed a table of specific complex traits, cross-referenced by different ancestry groups, indicating status of recent natural selection. The authors' results imply that different population groups have been experiencing differential selection over the last ~10k years: different selection pressures in different geographical locations. There were many talks at ASHG covering related topics, with similar conclusions. Advances in computational and statistical methods, together with large datasets, make it possible now to seriously investigate differential selection in recent human evolutionary history.

Given such results, how are researchers to respond when asked to categorically exclude the possibility of genetically mediated average differences between groups? 

We are scientists, seeking truth. We are not slaves to ideological conformity.
Building genealogies for tens of thousands of individuals genome-wide identifies evidence of directional selection driving many complex human traits.

S.R. Myers 1,2; L. Speidel 1
1) Department of Statistics, University of Oxford, Oxford, United Kingdom; 2) Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

For a variety of species, large-scale genetic variation datasets are now available. All observed genetic variation can be traced back to a genealogy, which records historical recombination and coalescence events and in principle captures all available information about evolutionary processes. However, the reconstruction of these genealogies has been impossible for modern-scale data, due to huge inherent computational challenges. As a consequence, existing methods usually scale to no more than tens of samples. We have developed a new, computationally efficient method for inferring genome-wide genealogies accounting for varying population sizes and recombination hotspots, robust to data errors, and applicable to thousands of samples genome-wide in many species. This method is >10,000 times faster than existing approaches, and more accurate than leading algorithms for a range of tasks including estimating mutational ages and inferring historical population sizes. Application to 2,478 present-day humans in the 1000 Genomes Project, and wild mice, provides dates for population size changes, merges, splits and introgressions, and identifies changes in underlying evolutionary mutation rates, from 1000 years, to more than 1 million years, ago. Using our mutational age estimates, we developed an approach quantifying evidence of natural selection at each SNP. We compared resulting p-values to existing GWAS study results, finding widespread enrichment (>2.5-fold in Europeans and East Asians) of GWAS hits among individual SNPs with low selection p-values (Z>6), stronger than the 1.5-fold increase observed at nonsynonymous mutations, and with enrichment increasing with statistical significance. We found evidence that directional selection, impacting many SNPs jointly, has shaped the evolution of >50 human traits over the past 1,000-50,000 years, sometimes in different directions among different groups. These include many blood-related traits including blood pressure, platelet volume, both red and white blood cell count and e.g. monocyte counts; educational attainment; age at menarche; and physical traits including skin colour, body mass index and (particularly in South Asian populations) height. Our approach enables simultaneous testing of recent selection, ancient natural selection, and changes in the strength of selection on a trait through time, and is applicable across a wide range of organisms.

Of course, all good people abhor racism. I believe that each person should be treated as an individual, independent of ancestry or ethnic background. (Hence I oppose Harvard's race-based discrimination against Asian Americans and favor Caltech's meritocratic approach to admissions.)

However, this ethical position is not predicated on the absence of average differences between groups. I believe that basic human rights and human dignity derive from our shared humanity, not from uniformity in ability or genetic makeup.

As a parent it is obvious to me that my children differ in innate aptitudes, preferences, and personalities. I love them equally: it would be wrong to condition this love on their specific genetic endowments.

Here is another set of ASHG talks I attended, on related issues:
Impact of Natural Selection on the Genetic Architecture of Complex Traits

Moderators: Shamil Sunyaev, Harvard Med Sch & Brigham & Women’s Hosp, Boston
Laura Hayward, Columbia Univ, New York

Evolution and maintenance of complex traits under natural selection has been a long-standing area of genetic research. Polygenic adaptation, stabilizing selection, and negative selection on new mutations can substantially impact the genetic architecture of diseases and complex traits, via direct selection on traits that are correlated with fitness and/or via pleiotropic selection. New methods are being developed to detect the action of natural selection at different time scales, including selection in contemporary humans. This session will discuss recent work on methods that analyze data from large cohorts to detect natural selection and evaluate its impact on diseases and complex traits. The application of these methods has substantially improved our understanding of polygenic disease and complex trait architectures, informing efforts to identify and interpret genetic variation affecting diseases and complex traits.

10:30 AM Polygenic architecture and adaptation of human complex traits. J. Pritchard. Howard Hughes Med Inst, Stanford.

11:00 AM Detection and quantification of the effect of selection and adaptation on complex traits. P. Visscher. Univ Queensland, Brisbane, Australia.

11:30 AM Observing natural selection in contemporary humans. M. Ilardo. Univ Utah & UC Berkeley.

12:00 PM Impact of negative selection on common variant disease architectures. A. Price. Harvard TH Chan Sch Publ Hlth, Boston.
More papers on recent natural selection and human complex traits:

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