Archive for the ‘Genetics’ Category

Skinny Genes Identified

09 Jan

Some very interesting stuff concerning body weight / body mass index (BMI) is coming out of the deluge of data resulting from more efficient genome sequencing. In particular, I have found two recent articles of great interest:

Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nature Genetics, Volume:43, Pages:753–760. Year published: (2011).

Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.  Nature, Volume:478, Pages:97–102. Date published: (06 October 2011).

The first article identifies a variation of the IRS1 gene linked to a low percentage of body fat. Not surprisingly, the article also corroborates my own experience that thinness, and especially extreme thinness, does not equal healthiness. Indeed, the researchers in this study found that people with the IRS1 variation leading to lower body fat still had high blood sugar and cholesterol levels — two important factors in the development of diabetes and heart disease. This may be due to the fact that while people with the “lean” IRS1 variant had lower levels of subcutaneous fat, they also had higher levels of visceral fat.

And that’s just the tip of the iceberg.  The second article is even more interesting. As reported in’s featured article Skinny Genes: Are Some People Born to be Thin?:

More recently, researchers from University Hospital in Lausanne and Imperial College London, in collaboration with a wide network of scientists and clinicians, looked at the DNA of over 95,000 people and found a 28-gene region that also relates to BMI: an extra copy of the region indicated extreme thinness, while a deletion of the region increased the risk of morbid obesity (typically, there are two copies of all genes—one from the mother and one from the father—but genetic mutations sometimes delete a gene or make too many copies of it).

Holy shmoly! Being a member of, and having access to my raw genetic data, I immediately set forth in an attempt to find out if I have the duplication in question. Unfortunately, 16p11.2 is a rather large region consisting of 6,627,240 base pairs and 284 SNPs of 23andme data, and I can’t narrow down the SNPs in question without obtaining the article (anyone with a subscription to Nature out there wanna help me out?).

Importantly, this same region was found to play a role in schizophrenia and autism, with a duplication being associated with schizophrenia and a deletion with autism. This interests me greatly, since certain personality types and psychological profiles have been thought to be correlated with particular body types since the earliest days of medicine.

Indeed, my (very purposeful) use of the term “ectomorph” to describe a thin body type is in reference to the theory of constitutional psychology developed by William Herbert Sheldon in the 1940s (although ideas relating psychological profiles to body type can be found long before his time). In short, heavy people (endomorphs) are relaxed, even-tempered, and good-humored (i.e., “fat and happy”), while thin people (ectomorphs) are anxious, moody, and emotionally sensitive. The in-between (mesomorph) is balanced, energetic, and adventurous. These traits supposedly varied due to the ratio of body mass to nervous system.

As you may easily surmise from the brief Wikipedia entries linked above, Sheldon’s work has been handily dismissed by modern medicine. In the never-ending debate of Nature vs. Nurture, the past few decades have leaned heavily toward Nurture — the implication being that “the environment” is the cause of our psychological distresses and issues, and that we need only change our environment in order to conquer our problems.

With the dawn of genetic research rising, now is the perfect time to re-evaluate such associations. Although Sheldon’s own view that “physique equals destiny,” may be extreme, and his generalizations simplistic, dismissing the possibility that certain physical and psychological characteristics may be intrinsically related simply because it makes us uncomfortable may be throwing the baby out with the bath water. As someone who has struggled with generalized anxiety disorder (GAD) since childhood, and a very characteristic “Type A” personality type, I would be more than happy to know for certain that these things are, by and large, genetically driven rather than just some peculiar flaws that I should somehow be able to overcome by sheer willpower.

The Skinny

Life as an extreme ectomorph