This document discusses the genetics of eating behavior and its relationship to obesity. It begins by outlining that eating behavior is influenced by physiological, psychological, social, and genetic factors. It then reviews several specific genetic influences on eating behavior, including Prader-Willi syndrome, LEP and LEPR genes associated with monogenic obesity, MC4R gene mutations linked to increased appetite and food intake, and variants in the FTO and GAD2 genes associated with obesity risk. Additional sections cover the genetics of taste preferences and their influence on food choices, as well as how genes related to hormones like ghrelin and CCK may impact meal size and selection. The document concludes that personalized treatment approaches targeting genetic mutations and behaviors could help

1. Genetics of eating
behavior
Maria Vranceanu
“Iuliu Hatieganu”University of medicine and Pharmacy, Cluj
Napoca

2. • why we eat?
• the motivational factors driving food
choices?

3. Eating behavior is a complex interplay of
physiologic, psychological, social, and
genetic factors that influence meal timing,
quantity of food intake, and food
preferences.

4. Review
• genetic influences of eating
behavior and how these relate to
obesity
• genetics of taste
• meal size and selection

5. The study of eating behavior
attempts to define:
•eating patterns and food preferences
•explain why there is gravitation toward
specific behaviors and food choices
•aims to develop approaches to bring about
effective changes in modifiable behaviors.
•Knowledge of the biological mechanisms
guiding eating behavior can provide
effective treatment targets for obesity and
associated disorders.

6. Prader Willi syndrome
a deletion of the 11-13q region of chromosome 15
characterized by hypotonia and poor feeding in early infancy, cognitive, motor
and behavioral impairment
followed by insatiable hunger and the development of morbid obesity and
diabetes during childhood

7. LEP and LEPR genes monogenic obesity

8. •the most common genetic cause of human obesity
•SNP (rs17782313), located downstream of MC4R, is confirmed
to be associated with overweight and obesity. The minor allele
(C-allele) of this SNP is believed to have reduced MC4R
expression when compared to the major allele (T-allele).
•The loss of function MC4R mutations lead to its carrier’s
increased appetite in childhood. A typical feature of the
affected individuals is hyperphasia, insatiable appetite. A
typical meal of mutation carriers contains about three times the
number of calories than that in non-mutation carrying siblings.
•Consistent with the hyperphagia eating behaviors of MC4R
loss-of-function mutations carriers, carriers of the C-allele of
the MC4R SNP rs17782313 eat larger amounts of food, snack
more frequently, like foods containing more fat content, and are
characterized as having weak satiety when tested with eating
behavior questionnaires (Choquet & Meyre. 2011; Cecil et al.,
2012).
MC4R GENE MUTATION

10. GAD2 (glutamate decarboxylase 2)
a positional candidate gene for morbid obesity on Chromosome 10p11–12
GAD2 gene encodes for the glutamic
acid decarboxylase enzyme (GAD65),
which is implicated in the formation of
the gamma-aminobutyric acid (GABA), a
neurotransmitter involved in the
regulation of food intake
In women, a SNP (rs992990; c.61450
C>A) was associated with disinhibition,
emotional susceptibility to disinhibition
and susceptibility to hunger.
Another SNP (rs7908975; c.8473A>C)
was associated with carbohydrate
intakes, disinhibition
(SNPs) +61450 C>A and +83897 T>A
associated with morbid obesity
allele of SNP -243 A>G increased six
times GAD2 promoter activity and is
associated with higher risc of obesity

11. Genome-wide association studies (GWAS) have reliably established
that SNPs within the first intron of FTO are robustly associated with
increased BMI and adiposity across different ages and populations.
homozygous for the risk A allele of FTO rs9939609 have a 1.7-fold
increased risk for obesity compared with homozygous with T allele .
Subjects homozygous for the obesity-risk A allele exhibit overall
increased ad libitum food-intake, particularly fat consumption , and
impaired satiety .
preschool AA children exhibit obesity-prone eating behaviors, including
increased food responsiveness and a tendency to eat in response to
external cues.

12. Meal selection and size?
• Research into meal size and selection is
especially complex as socioeconomic
environment, learned eating behaviors,
physiologic conditions such as
depression, and even medical
treatments can all influence appetite
and food selection, independent of
genetics
• however meal quantity, frequency, and
timing are thought to be at least in part
under genetic control.
• The study of genetic variants in
digestive neuroendocrine hormones,
such as CCK, leptin and ghrelin, are
providing new insights into how these
hormones and their genetic variants
may be involved in pathways regulating
appetite and eating behavior

13. Ghrelin, a 28-amino acid
peptide, produced by the
stomach and pancreas
involved in promoting meal
intake and hunger through
receptors in the hypothalamus.
Plasma ghrelin levels rise pre-
meal and are suppressed by
food intake.
GHRL is located on
chromosome 3.
A common variant, Leu72Met
has been associated with
obesity, metabolic
syndrome, and binge eating.

14. CCK( cholecystokinin)
released in response to lipids and promotes rapid post-prandial
satiety in contrast to the long term action of leptin.
CCK variants (rs6809785, rs7611677,
rs6801844, and rs6791019) were found to be
more associated with extreme meal size but
not increased snacking behavior

15. Five tastes are recognized by
humans: sweet, bitter, sour, salty,
and umami
• Food preference
and intake is
influenced by sweet
and bitter taste.
Genetic of taste

16. Bitter
taste
Individuals who are
particularly sensitive to
bitter compounds tend to
avoid the bitter taste of
beer and alcohol, and
avoid cigarette smoking
as well.
Bitter taste as well as
preference for sweet and
fat guide ingestive
behaviors, and have been
linked to obesity, and
these food preference
traits may in part be
genetically determined.

17. Bitter taste
Genes
TAS2Rs:
TAS2R38,
TAS2R5,
TAS2R16
Influence on Ingestive
behavior
Vegetable avoidance,
increased fat and
sweet intake
disinhibited eating
behavior among
women
Alcohol dependence

18. Emotional eating is driven by emotional cues like depression,
anxiety, happiness, sadness, and boredom rather than
hunger. By engaging in emotional eating, we are
subconsciously seeking comfort or pleasure from food.

19. DRD2 and OPRM1 genes function in the brain reward system.
Variations in these genes are associated with
emotional eating and weight gain.

20. The DRD2 gene is a key
player in the dopamine
neuronal circuits.
Dopamine is the “feel good”
neurotransmitter that motivates
people for pleasure.
A variation in the DRD2
gene, Taq1A1, results in a
reduced dopamine function
in the brain.

21. OPRM1 gene is a key play in the opioid neuronal circuits.
Activation of the opioid neuronal circuits leads to the production
of dopamine.
Activities of the opioid system also determine how much you
enjoy the pleasure.
These neuronal circuits interact with each other and with other
neuronal circuits to produce an overall “reward value” of a food.
This “reward value” influences eating behaviors.
People suffering from binge eating disorder appear to be highly
active in both the dopamine and the opioid systems.
A variation of OPRM1 increases activity in the opioid neuronal
circuits. Carriers of this variant have greater risk for drug
addiction
Risk variant: 118G+

22. DRD2, OPRM1 and Binge Eating Disorders
In a study of obese populations, the combination of the
A2A2 genotype of the DRD2 gene and the G-allele of the
OPRM1 gene (A-/G+ ) was the most frequent one in the
group characterized by obese and binge eating(Davis et
al., 2009).
These data suggest that the A1-/G+ combination is the
cause of binge eating. Since the A1- is associated with a
higher dopamine D2 receptors and the G allele is
associated with an increased opioid activation, the
A1−/G+ combination reflects a hedonic-enhanced
genotype combination, one that increase the risk for
binge eating.

23. Conclusions
Personalized medicine, tailoring pharmacologic and behavioral therapy
to an individual’s genetic code, is an emerging practice.
Applications of research of the genetics of eating behavior may lead to
individualizing therapies targeting specific genetic mutations and
behavioral interventions addressing eating behaviors.
Once the role of specific gene variants in pathways involved in specific
behaviors or food responses are well established, treatment could be
individualized toward modifying these behaviors
and pharmacologic modalities developed to modify molecular pathways
involved.

24. Vranceanu.Maria@umfcluj.ro