Multi-Factorial Like Crazy

As we have seen, it is known that genes influence a person’s brain and behavior. Surely, they influence obesity, but after that, almost everything else is a big mystery. Which genes are mutated? Do they switch other genes off or on? Do other genes affect them? Can they be prevented from doing whatever it is they do?

The beginning of a dispatch from the University of Iowa, about the biological pathways associated with eating disorders, their neurological basis, and the possibilities of gene editing, is fairly captivating:

Giving mice a gene mutation linked to eating disorders in people causes feeding and behavior abnormalities similar to symptoms often seen in patients with eating disorders. Only female mice are affected by the gene mutation, and some of the abnormalities in the female mice depend on whether they are housed alone or together with other mice.

There is a lot in that paragraph to unpack. Why only females? Why does it make a difference if they live solitary or have roommates? Are mice anything like people?

The same report says that a neurotransmitter called glutamate is related to depression, obsessive-compulsive disorder, and feeding habits. Here is an interesting tidbit:

The genetically altered female mice were more anxious and irritable when they were in a group living situation than when they were individually housed and seemed to find social interaction less rewarding.

A 2016 article about genome-wide association studies (GWAS) for adiposity enumerates the “five waves of discovery for BMI,” or body mass index, the most widely used metric in the obesity field. A major player is the gene known as FTO, which as of two years ago was still the locus of obesity susceptibility known to have the greatest effect on BMI.

The second wave had to do with the MC4R and the leptin signaling pathway, and there will be more about that later. Seven studies were done which, together, confirmed the FTO locus association.

The third wave involved a consortium called the Genetic Investigation of Anthropometric Traits that confirmed other things. The fourth wave was about the identification of 18 additional novel loci associated with BMI.

This sounds exciting, but it’s all discouragingly slow. Authors Radha Venkatesan and Mohan Viswanathan wrote:

At this stage, a total of 32 loci associated with BMI were identified. However, the combined effect of the 32 loci is only 1.45%. Hence, predicting obesity using the risk alleles of these BMI loci is not accurate. These 32 loci together did not show any clinical application to discriminate between obese and nonobese individuals.

The fifth wave consisted of confirming the 32 BMI-associated loci, and “7 new loci were identified which explained an additional 0.09% of the variability in the BMI.” The same authors also wrote:

The escalating frequency of obesity during the past few decades is due to environmental factors such as sedentary lifestyle and overnutrition, but who becomes obese at an individual level is determined by genetic susceptibility. Understanding of the molecular cause of obesity is still in its infancy.

Around this time, Gina Kolata wrote for The New York Times that more than 25 genes had been found with effects so powerful that “if one is mutated, a person is pretty much guaranteed to become obese.” She interviewed Dr. Ruth Loos of Mount Sinai’s Icahn School of Medicine, who said that 300 genes had been discovered whose alteration could contribute to obesity. Each one on its own might not have much effect, but if a person happened to “inherit a collection of them,” they could cumulatively make quite an impact.

Your responses and feedback are welcome!

Source: “Eating disorder gene alters feeding and behavior in female mice,”, 10/13/18
Source: “Obesity — Are we continuing to play the genetic ‘blame game’?,”, 11/18/16
Source: “One Weight-Loss Approach Fits All? No, Not Even Close,”, 12/12/16
Photo credit: NIMR London on BY

Leave a Reply

Your email address will not be published.

FAQs and Media Requests: Click here…

Profiles: Kids Struggling with Weight

Profiles: Kids Struggling with Obesity top bottom

The Book

OVERWEIGHT: What Kids Say explores the obesity problem from the often-overlooked perspective of children struggling with being overweight.

About Dr. Robert A. Pretlow

Dr. Robert A. Pretlow is a pediatrician and childhood obesity specialist. He has been researching and spreading awareness on the childhood obesity epidemic in the US for more than a decade.
You can contact Dr. Pretlow at:


Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

Food & Health Resources