Researchers have identified new genes that determine why lean people stay slim and why overweight people gain more weight. These are new pieces in the puzzle that should bring a solution to obesity closer.
DNA
Some of the most exciting developments of the last decade come from breakthroughs in research on human DNA. It’s a difficult matter to explain. Fortunately, we have a top scientist in the Netherlands who recently gave a beautiful description of DNA. ‘In total, you have about 60 grams of DNA inside you,’ said Robert Dijkgraaf during his most recent lecture for DWDD University [1]. ‘Like the instructions in an IKEA construction kit,’ he described it. A two-meter long thread with codes in every cell containing instructions for the cell. To illustrate how much information is hidden in the 60 grams of DNA, he translates the thread into books. In this case, ‘3,000 parts of Harry Potter.’ Written in a molecular alphabet consisting of four letters: A, C, G, and T. Four possible molecules that together form about 3 billion letters. That two meters of DNA in every cell is coiled up in the chromosomes and contains about 20,000 instructions (or ‘construction kits’). The first phase of mapping the human genome was completed in 2000.Today, we are learning the language with which God created life. President Bill Clinton
‘Genetically Determined’
Now, it’s an incredibly difficult challenge to figure out which of those 20,000 instructions exactly influence which trait. A difficult task, but one that is possible now that we can rewrite the instructions in the DNA. For example, by changing an ‘A’ to a ‘C’. You immediately understand how difficult that is. You modify a worm with a genetic alteration and then hope that it shows a measurable deviation. This way, you can find out that it suddenly can defecate twice in a row and apparently you’ve discovered a ‘poop gene’ [2]. Or you discover which gene is responsible for wet or dry earwax. A beautiful example by Robert Dijkgraaf. Many genes have overlapping tasks, so you don’t immediately see a difference when you disable one of those genes. As mentioned, it’s an incredibly difficult task. Nevertheless, small steps are being made. Also when it comes to the genes that influence your body weight.DNA and Obesity
What scientists are doing now, among other things, is searching for correlations by linking DNA to other information. In this way, researchers from Cambridge, with the largest study (of this type) to date, tried to answer an increasingly common question: Why do some people stay slim while others easily gain weight [3]? Their research shows that the ‘genetic odds’ are against people with obesity and in favor of slim people. This confirms what many have been saying for decades: That weight is largely determined by genes. They also mention a point that I happened to make just last week in an article about condemning people with obesity: If you’re slim or overweight, it often has much less to do with personal effort than we often assume. This was demonstrated in studies with twins, among others. Previous studies mainly looked at people with obesity and searched for similarities in genes. In those studies, hundreds of genes were found that increase the likelihood of someone getting overweight. Defective genes have also been found in some people that can lead to severe obesity at a young age.Fattening Genes
In the Study Into Lean and Thin Subjects (STILTS), the researchers wanted to look at slim people and their genes. They found 2,000 slim, healthy participants in Great Britain. Saliva samples were taken for DNA analysis from various practices in the country. In addition, participants were asked to complete questionnaires about their health and lifestyle. Last week, the results were published in PLOS Genetics. The researchers compared the DNA of about 14,000 people. That of 1,622 of the slim participants, 1,985 people with severe obesity, and 10,433 people with normal weight as controls. The team found several genetic variations that were already known to play a role in obesity. In addition, they found new genetic areas that play a role in severe obesity. Finally, they also found genetic variations that play a role in the weight of the slim participants. These specific genetic variations can help zoom in on genes and biological processes that help to be or remain slim.Genetic Risk Score for Obesity
They then added up these genetic variants to create a genetic risk score for obesity. As expected, people with a high score had a higher weight than people with a ‘normal’ score. Moreover, it turned out that slim people had a low score, compared to people with normal weight. They had fewer genetic variants that increase the risk of obesity.This research shows for the first time that healthy thin people are generally thin because they have a lower burden of genes that increase a person’s chances of being overweight and not because they are morally superior, as some people like to suggest. It’s easy to rush to judgement and criticise people for their weight, but the science shows that things are far more complex. We have far less control over our weight than we might wish to think Professor Sadaf Farooqi, University of CambridgeIn the study, 74 percent of slim people had a family history of slim and healthy ancestors. If researchers succeed in finding all the genes that help with this, new strategies can be devised for people who are less lucky with their genes.
Sources
- dewerelddraaitdoor.bnnvara.nl/nieuws/nieuw-college-robbert-dijkgraaf-de-toekomst
- nemokennislink.nl/publicaties/30-punt-000-genen-en-wat-nu/
- Fernando Riveros-McKay, Vanisha Mistry, Rebecca Bounds, Audrey Hendricks, Julia M. Keogh, Hannah Thomas, Elana Henning, Laura J. Corbin, Stephen O’Rahilly, Eleftheria Zeggini, Eleanor Wheeler, Inês Barroso, I. Sadaf Farooqi. Genetic architecture of human thinness compared to severe obesity. PLOS Genetics, 2019; 15 (1): e1007603 DOI: 10.1371/journal.pgen.1007603
