Week 4

Question 1

What does the line in a manhattan plot mean?

Answer 1

That the association is statistically significant

Question 2

Do you need a control group in a GWAS study?

Answer 2

No, because the variables are continuous

Question 3

What are GWAS adjusted for?

Answer 3

Gender, age and ethnicity

Question 4

What is the missing heritability problem?

Answer 4

GWAS only explain a little of the variation, twin studies estimations are too high or just looking at SNPs is too easy

Question 5

What is mendelian randomization?

Answer 5

People are randomized by their genetic code. If there is an association between the genotype that predicts exposure, the exposure is causal for the event.

Question 6

What is a big assumption with mendelian randomization?

Answer 6

The SNP does not influence the disease risk other than the exposure of choice.

Question 7

What id DNA methylation?

Answer 7

An added methylgroup to a CpG site.

Question 8

What is measured with EWAS?

Answer 8

The proportion of methylated CpG sites

Question 9

What are challenges with EWAS?

Answer 9

tissue specific
Cell type specific
Unclear causation
Need high number of people
Confounding
Potential role of genetics

Question 10

What dietary factors can be methyl donors?

Answer 10

Folic acid and B12

Question 11

What foods have folic acid? And what is folic acid associated with?

Answer 11

Green leafy vegetables, meat, fruit and grains

Lower stroke risk and CV death

Question 12

What is the barker hypothesis?

Answer 12

Adverse nutrition in early life causes a higher risk of diseases later in life

Question 13

What happens in the different trimesters of pregnancy if the mother is starving?

Answer 13

1st and 2nd: more diseases later life

3rd: lower birth weight

Question 14

What genes are affected in the hunger winter study?

Answer 14

Growth, development and metabolism

Question 15

What are the sampling methods of the microbiome?

Answer 15

Model organisms
Patients with ileostomy
intestinal catheters
Novel devices
faecal samples

Question 16

What are the sequencing methods of the microbiome?

Answer 16

rRNA gene profiling: look at a specific part of MB
Meta genomics with DNA: sequence all present DNA
16rRNA sequencing; can only differentiate between different genus, not species
Meta transcriptomic with RNA: for DNA activity, you don’t know from which bacteria the RNA was from

Question 17

What is the difference of MOs in the large and small intestines?

Answer 17

Small: low density and diversity, harsh environment, short transit time, nutrient rich
Large: large bacterial load, high diversity, no digestive secretions, nutrient poor, longer transit time.

Question 18

What happens with the MB with obesity and DM?

Answer 18

Less MO diversity

Question 19

What does fibre do with the MB?

Answer 19

Increase diversity

Question 20

What does FT do in humans?

Answer 20

Improve insulin resistance (causality and long term effects not known), no effect on body weight.
Chrohns disease patients benefit
For curing clostridium infections

Question 21

Does the environment influence the MB?

Answer 21

Only a little, mainly diet

Question 22

How long does it take to change MB?

Answer 22

Extreme changes, a few days
stable changes 6-9 months
Less diversity: to next generations (mainly plant fibre degradation)

Question 23

What influence does the MB have on the host?

Answer 23

Digest indigestibles
Produce energy
Produce signalling molecules
Fermentation of fibre

Question 24

What happens when the MB ferment fibres?

Answer 24

Production of short chain FAs -> improve colonic health and play a role in

• energy balance
• regulation of satiety, appetite and fat metabolism
• increase biodiversity

Question 25

What happens when you have a high intake of animal foods?

Answer 25

Conversion of choline and carnitine to TMAO by MB
Increases CV events by:
- Altering cholesterol mechanism
- Increasing development of atherosclerosis