Gene Expression

It is well known that different ethnic groups vary when it comes to diseases such as Type II Diabetes. Or, more specifically they vary in terms of risk, all things equal (if you use an online Type II Diabetes calculator you’ll see immediately as they sometimes have a parameter for ethnicity). American blacks for example are heavier than American whites. This seems to be true even when you control for socioeconomic status (though as Oprah once said, “You don’t need to do a ‘study’ to figure that out”). There has been research on genetic loci correlating to obesity in European populations before, but there is now a new one which looks at African Americans, and tries to ascertain whether some of the loci might be unique to them because of their racial ancestry.

Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X:

Obesity is about 1.5-fold more prevalent in African Americans than European Americans. To determine whether genetic background may contribute to this observed disparity, we scanned the genomes of African Americans, searching for genomic regions where obese individuals have a difference from the average proportion of African ancestry. By examining genetic data from more than 15,000 African Americans, we show that the proportion of European ancestry is inversely correlated with BMI. In obese individuals, we detect two loci with increased African ancestry on chromosome X (Xq13.1 and Xq25) and one locus with increased European ancestry on chromosome 5 (5q13.3). The 5q13.3 and Xq25 regions both contain genes that are known to be involved in appetite regulation. Our results suggest that genetic factors may contribute to the difference in obesity prevalence between African Americans and European Americans. Further studies of the regions may identify the causative variants affecting susceptibility to obesity.

The sample here is ~20% European in ancestry, in line with a large body of research on African Americans. Additionally, there is variance in the black community in terms of how much European ancestry an individual has (e.g., a rule of thumb is that around 10% of black Americans are actually 50% or less African in ancestry). This study find a weak but statistically significant negative correlation between European ancestry and Body Mass Index (BMI), ρ = −0.042 & P = 1.6×10−7. Here’s the figure (modified to fit on the screen) which illustrates it:

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Let’s jump to the part on where they find associations between obesity and particular genetic variants:

The residual association of local ancestry with BMI after adjusting for genome-wide ancestry remained significant at both Xq13.1 (P = 1.9×10−7) and Xq25 (P = 4.1×10−6) (Model 2 in Table 3), indicating that local ancestry had an effect on BMI above and beyond genome-wide ancestry. Both associations were nominally genome-wide significant (P = 1.9×10−4 and P = 4.1×10−3) after conservatively correcting for 1,000 hypotheses tested. A naive analysis suggests that each additional copy of a European ancestral allele at either the Xq13.1 or the Xq25 peak is independently associated with a BMI decrease of ~0.1 Z-score units on average (equivalent to ~0.64 kg/m2 and accounting for 0.3% of the variance in BMI, after adjusting for age, age-squared, sex and study). The true genetic effects are expected to be somewhat weaker because of discovery bias.

There was a weak correlation between total European genome content in African Americans. But here what they have found are possible genetic regions with elevated European ancestry, that is genes which are distinctively European in form which some African Americans carry. These genes seem to correlate with reduced BMI. The key point is that you have to zoom in on a finer grained level genomically because total ancestry isn’t always going to be a good predictor. But here’s an interesting find:

The association at the 5q13.3 peak was particularly interesting in that it did not achieve statistical significance until the genome-wide estimate of European ancestry was added into the analysis. This was presumably because the locus effect was in the opposite direction to the genome-wide ancestry effect (thus, the effects cancel in the unadjusted analysis). Each additional copy of a European ancestral allele at 5q13.3 was significantly (P = 5.8×10−7) associated with an increase in BMI of 0.09 Z-score units (naively equal to ~0.59 kg/m2, accounting for 0.3% of the variance in BMI), which was nominally significant (P = 5.8×10−4) after correcting for the approximately 1,000 independent hypotheses tested.

In other words, the overall trend obscured this particular signal. In any case the authors note that there is research which suggests that obesity is ~40% heritable, so those heritable genetic components may vary between populations (as well as within). Studies in diverse populations, including admixed ones, obviously are going to be important pieces of the puzzle.

Citation: Cheng C-Y, Kao WHL, Patterson N, Tandon A, Haiman CA, et al. (2009) Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X. PLoS Genet 5(5): e1000490. doi:10.1371/journal.pgen.1000490

Comments

  1. #1 Constance
    May 23, 2009

    Studies such as this are needed in the fight against disparities in the African American community. As a diabetes educator I am often asked why African Americans develop type 2 diabetes at a greater rate then their European counterparts….this helps to answer that question.

  2. #2 diana
    May 23, 2009

    And I wonder if the European ancestry they have is Northern European.

  3. #3 mary
    May 24, 2009

    I really don’t think obesity is related to race. It’s just related to your diet. So right diet is the most important. Here is about Chinese holistic diet.
    http://www.healthy-chinese-recipe.com/obesity-diet-recipes-low-fat-low-calorie.html

  4. #4 maciano
    May 24, 2009

    Hey Mary,

    1) What you ‘think’ — or believe you must think — is not a good reason to criticise a paper, you need to come up with different proof, i.e. scientific research, backed up with logic and plausibility. You don’t do that. (“Chinese holistic diet”.. Are you kidding me?)

    2) Low-fat & low calorie diets never work in the long run. You’ll always be hungry and finally you will eat again — move back to your old weight (and then some.) If blacks want to lose weight for real, they should, like any obese human, move on to a high fat/protein diet.

  5. #5 musaki
    May 24, 2009

    But, but, but I thought that Sandra Scarr disproved that percent European ancestry was a relevant explanatory variable with her sample of size 144! How could these thought criminals have decided to include it as a colum in the regression equatoin?

  6. #6 Paul Blake
    May 25, 2009

    I will give you a real possibility, sorry no stats. I remember when a marshmallow was a marshmallow, do you? Have you tried to roast a marshmallow lately, good luck? What has happened to the good old marshmallow, the same thing that has happened to most of our food. When we were not paying any attention they took the marshmallow out of marshmallows but kept the price moving gradually upward. What is in the marshmallow today, artificial colour, artificial flavour, corn syrup, dextrose, gelatin, modified corn starch, sugar, tetrasodium pyrophosphate, sounds like a gut bomb to me. It still looks like a marshmallow and they still call it a marshmallow but it is obviously not. This kind of slow changing of ingredients has gone on food industry wide; it remindes me of the Trojan horse. Now suddenly everyone is noticing that gee, we have an obesity epidemic and a whole lot of other epidemics. Genetics is the weak answer medical science wants you to buy into so they can research it and make more drugs. Besides, how does the genetics of an entire country change in a matter of years? I am sure that your doctor cares but does the industry care? Why should they care; more sick people means more money in their pockets. Try this; on a piece of paper write down 10 diseases you can think of then do a Google search of each one of them and add the word epidemic to it. You will see that the majority of them are at epidemic numbers of 1 in 4 people will get this disease. If you think that this is ok; then you must be on a lot of drugs yourself. Paul

  7. #7 Martin Regnen
    May 25, 2009

    This post sure seems to be attracting interesting comments, so let me throw one out also: we don’t know if the difference in BMI is due to difference in fat mass or the fact that white folk have flat asses. More European ancestry may well just mean a couple pounds less muscle in the glutes.

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