Gene Expression

Dienekes reports on an abstracts for paper presentations at the ESHG 2009. This was is particularly interesting:

European Lactase Persistence Allele is Associated With Increase in Body Mass Index

J. A. Kettunen et al.

The global prevalence of obesity, usually indexed by body mass index (BMI) cut-offs, has increased significantly in the recent decades, mainly due to positive energy balance. However, the impact of a selection for specific genes cannot be excluded. Here we have tested the association between BMI and one of the best known genetic variants showing strong selective pressure: the functional variant in the cis-regulatory element of the lactase gene. We tested this variant since it is presumed to provide nutritional advantage in specific physical and cultural environments. We found that the variant responsible for lactase persistence among Europeans was also associated with higher BMI in a Nordic population sample (p = 1.3*10-5) of 15 209 individuals, the size of the effect being close to that of FTO. We tested the effect of population stratification and concluded that the association was not due to population substructure.


The mutation which results in lactase persistence is one of the canonical examples of recent human evolution driven by natural selection. It looks as if over the past 10,000 years several populations have developed this trait independently due to selective pressures, in particular the nutritional benefit of adult digestion of the lactose sugars in milk. The fact that in northern European populations where ~95% of people are lactase persistent there is a difference in body mass which tracks this trait is intriguing, as it suggests the reasons why this new ability was driven to fixation so powerfully. In the pre-modern world extra caloric intake would probably have been a difference between life and death, and body fat has also been related to female fertility.

Comments

  1. #1 Ray Works
    May 11, 2009

    As someone with Nordic ancestry (Danish/North German/Scottish/English in order of decreasing amounts) I read the article with personal interest.

    I am lactose intolerant (one of the lucky ones I guess) and my BMI is still over 26.

    Not saying a single datapoint invalidates a study, but I would note that there are other factors in obesity besides lactase tolerance. Correlation does not make causation.

  2. BMI is infamous for not being able to tell the difference between someone who has a lot of weight because they are fat and someone who has a lot of weight because they are muscular.

    I wonder if they have any data on whether the increased BMI is more due fat or muscle. And wonder if they have any data on the Somatotype ratios of the population.

  3. #3 Rachel
    May 11, 2009

    This is one of those discoveries that could be misleading to those seeking obesity magic bullets. I’m glad you mentioned dairy as an extra calorie source. It seems here that that the capacity to digest lactose would cause different diet choices, often those higher in fat. I would think this would be more of a case of diet affecting bmi than the enzyme it’s self. It would be neat to see a study looking for a similar correlation to decreased bmi in people who voluntarily exclude dairy from their diets just to clarify the results.

  4. #4 razib
    May 11, 2009

    rachel, yes, i didn’t assume that the enzyme was causually related like FTO. rather, i have heard that lactose is 1/3 of the calories in milk. so if you can’t digest that 1/3, you take in 1/3 less calories, and in a culture where drinking milk is normative.

  5. #5 Sandgroper
    May 11, 2009

    BMI is only a reasonable proxy for fatness at a population level. At an individual level it can be pretty meaningless. This study was on a big enough sample such that it could reveal a relationship between nutrition from dairy and body mass in a population where dairy consumption is normative, i.e. if you can digest lactose you are going to get more calories from lactose than if you can’t. Seems kind of self-evident. On a sample as big as 15,000, BMI probably is a fair proxy for fatness, given that they have eliminated population structure as a confound.

    What interests me are the national obesity rates in the post above titled “Not all causal relationships are created equal”, where BMI > 30 has been taken as a proxy for obesity, which at a population level is reasonable. Germany and the Scandinavian countries are below 15% for BMI > 30, they have high % of population with lactase persistence, and they are (now) the tallest people in the world.

    If I had data on dairy consumption, I would do the numbers on that, lactase persistence and height at the population level. Could be interesting. For constant body mass, BMI reduces with increase in height, of course. Duh.

  6. #6 Lilian Nattel
    May 11, 2009

    That’s interesting–as is the comment on height. Is lactose intolerance associated with overall smaller stature?

  7. #7 Dina Ralt
    May 11, 2009

    it is not just the correlation that is interesting, for me personally it was so relevant…milk abstinance tripled!!! the rate of my losing weight. see the fig.
    http://nettingno.blogspot.com/2009/04/no-milk-today.html

  8. #8 Hamilton
    May 12, 2009

    The situation is now very difficult and many people do not really know what to do, but now we must get down to analyze each of us and see if we can get ahead, as everything depends on oneself, there are ups and downs but the important thing is that while there is life there is hope, a few days ago I read in findrxonline that antidepressants are the most common pills used in these cases but not many of them know the consequences …

  9. #9 pconroy
    May 12, 2009

    Sandgroper,

    Germans and Scandinavians are NOT the tallest people in the world. See this Nation Master link on height, where it shows that the tallest people in the world are:

    1. Dinaric Alps (17 yo):
    Male: 186 cms (6′ 1.1″)
    Female: 171 cms (5′ 7.3″)

    2. Netherlands (21 yo):
    Male: 183 cms (6′ 0″)
    Female: 170.6 cms (5′ 7.2″)

    I know the Dutch diet included huge amounts of dairy products, not sure about the Serb/Bosnian/Montenegran diet?

  10. #10 Ned in Zurich
    May 12, 2009

    Razib,
    it’s not just the calories in lactose that lactase-nonpersistent adults forgo. Were they to drink a liter of milk they would suffer severe diarrhea and flatulence as the lactose was digested by bacteria in the large intestine. In this case it’s best to eliminate milk from the diet almost completely.

  11. #11 Sandgroper
    May 13, 2009

    Paul – Yep, error acknowledged.

    The Dutch increase in height over the past century or so has been nothing less than spectacular. A Dutch friend told me that in the Netherlands they are now treating people with growth inhibiting drugs because they are getting too big and it is causing them problems. He is 6’1″ and said he was the smallest in his class.

    I only know about Croats. Not particularly high in dairy, but a lot of animal protein. Really a lot.

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