March 22, 2009

Admixture analysis in Central Europeans

Polish Genetics points me to a new paper in Nature which includes an admixture analysis of Central Europeans. The supplementary data is freely available (pdf).
The IARC study of lung cancer in central Europe was conducted with cancer institutes in 6 countries including Czech Republic (Prague, Olomouc, Brno), Hungary (Borsod, Heves, Szabolcs, Szolnok, Budapest), Poland (Warsaw, Lodz), Romania (Bucharest), Russia (Moscow) and Slovakia (Banska Bystrica, Bratislava, Nitra) between 1998 and 2002.
A little random deviation from the (1,0,0) (Europe, Africa, Asia) point in the triangle plot is expected, and this is visible along the Europe->Africa axis where the presence of any level of Sub-Saharan African ancestry seems improbable. A stronger degree of deviation along the Europe->Asia axis is consistent with a small degree of East Eurasian admixture in these mainly Eastern European populations.

Nature doi:10.1038/nature06885

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25

Rayjean J. Hung et al.


Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually1. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 times 10-10). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 times 10-20 overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines2, 3, and they bind to N'-nitrosonornicotine and potential lung carcinogens4. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets5.



  1. Those outliers would be Roma, no?

    Maybe some of them. But I don't think all.

  2. At K=3 South Asians cluster overwhelmingly with Europeans and not with East Asians. Roma are part South Asian part West Eurasian, so they will be even more similar to Europeans compared to East Asians. So, I doubt that the outliers are Roma.

  3. Forgive my ignorance, but what defines South Asia? Is this India and the Middle East? or more Cambodia, Thailand, and Vietnam?

  4. South Asia = Indian Subcontinent

  5. They may also be Altaic or Uralic remnants.

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  7. onur said,

    "They may also be Altaic or Uralic remnants."

    Uralic? I strongly doubt it. Most "Uralic" people cluster even more closely with Europeans than South Asians do. The only sort of "Uralic remnants" that might produce such a large degree of deviation toward the East Asian cluster should be the Siberian sort, i.e. Nenets, Enets, Nganasan, Selkup, Khanty, and Mansi, whose total population according to the 2002 census is an underwhelming 86,820 persons.

  8. AFAIK 4 of the 5 outliers come from Moscow, and may be people of fairly recent mixed Eurasian background. I don't know where the 5th one is from.

    2016 of these samples were also used in Heath et al. 2008, and compared to other Europeans. See second diagram here...

  9. I take it that "Africa" means sub-Saharan Africa?

  10. I've never heard Moscow to be considered part of "Central Europe"! I wonder how the map looks if the Moscow samples are removed.

  11. Perhaps the East Asian DNA comes from minority groups like the Uhlans aka Polish Tartars?

    Here is an image of some Polish Tartar soldiers

  12. I should also mention that my first wife was Polish, with parents from Poznan and Lvov, and told me that as a young child she ahd the Mongolian Blue Spot - even though she was a blue eyed blonde?!

  13. pconroy,

    Based on these Polish samples, Asian admixture in Poland is lower than in Germany, Norway, Sweden and Czech Republic, to name a few.

    You can read about that here...

  14. Are you sure about South Asia?

    The one known asian title in Central Europe in medieval time was "hakan" (or "khagan") for the chief of avars' state (Avarian Khaganate). In that context pconroy might be right about asian trace in polish armor.

    P.S. Don't mind "Moscow samples". :) Some people from Poland tend to consider russians being uralic-mongoloid mixture.

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  16. I superimposed this admix plot over the PCA from Heath et al 2008.

    (a and (b are the same, (b is just a much bigger version.

  17. Polak,

    I'd expect the Czech to have more East Asian DNA, as they probably have more Hungarian blood, and that would be the probable source IMO.

    As regards Norway and Sweden, I too would expect them to have more East Asian DNA, due to the putative migration of Huns, Alans and Sarmatians to that region over a millennium ago.
    Here is a very well researched article, by David Faux, on the Central Asian Roots of Scandinavia, where he links all the evidence togather, and verifies it vis Y-DNA analysis.

  18. I think Russia is hardly in Central Europe...

  19. Pconroy, I'm part Polish myself, and my oldest daughter had a very obvious-- and unexpected-- blue spot when she was a baby.

  20. Well anyway, I think it's pretty interesting to get only 5 outliers from 4,448 samples, especially as these are cancer patients and controls, and not people specifically chosen to represent their respective ethnic groups.

    The second plot I posted above uses the same samples, minus the cancer patients, but many more markers. It's quite nice in the way it shows the individual European countries. But the only inter-continental outlier there is one guy from Japan.

    It'd be really fascinating to get figures of admix rates for each of the several thousand people on that PCA, plus averages for each country. It looks like some of those British and Germans would have as much Asian influence as that subset of Russians, who are most likely of Finnic or Tatar origin. I'm just guessing, but that's probably the result of a colonial history in the east.


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