Complex diseases

Question 1

Genetic biomarkers what used for

Answer 1

diagnosis and prognosis, prevention, pharmacogenetics (identifying genetic variants that control efficacy and adverse events of drugs), new drug targets

Question 2

Give examples of complex diseases

Answer 2

asthma, breast cancer, heart disease, depression, schizophrenia, autism, arthritis, migraine, obesity diabetes

Question 3

What are properties of complex diseases

Answer 3

raised risk in families, no clear mode of inheritace, multiple genes contribute to disease risk, environmental effects also contribute, involve gene-gene and gene-environment interactions

Question 4

what kind of assessments conducted for genetic contribution to disorder

Answer 4

Twin studies estimate heritability (proportion of totla variance of trait caused by  additive genetic factors)
Family studies (whether there is increased risk for first degree relative compared to general population)

Question 5

What do Mendelian disorders involve and give examples of such diseases

Answer 5

rare variants, single gene disorders

Huntington’s, cystic fibrosis

Question 6

What kind of diseases have a mix of common and rare variants

Answer 6

breast cancer, alzheimer, ALS, epilepsy, autism

Question 7

What do common variant diseases involve and give examples of them

Answer 7

polygenic suceptibility to most disorders

cardiovascular disease, rheumatoid arthritis, schizophrenia, depression

Question 8

What kind of genes are breast cancers caused by and what are risk factors

Answer 8

major genes-BRCA1 and BRCA2 (high penetrance)
low risk genes: FGFR2, TNRC9, MAP3K1
risk factors: reproduvtive, menstrual, hormonal, lifestyle, physiological, imaging, family history

Question 9

Which genes cause Alzheimer’s

Answer 9

high risk genes-APP, PSEN1, PSEN2 (young onset, high risk families)
moderate risk genes-APOE allele e4, rare variants in TREM2 gene
low risk variants-SNPs in CLU, PICALM, CRU

Question 10

What are alleles of APO-E genes and how does its risk for Alzheimer’s compare

Answer 10

e4-increased risk
e3-baseline risk
e2-protective against alzheimer

Question 11

What method identifies genes for polygenic disorders and what does this study involve

Answer 11

genetic association study

tests whether presence of specific genetic variant increases risk of disease

Question 12

For case control study, what conditions must be true for cases and controls

Answer 12

Cases: affected with disease, need clinical criteria for inclusion study, geographic+ethnic background
controls: random population samples/unaffected individuals, geographic information
cases and controls must have similar genetic background

Question 13

How are case control study data analysed, what test is conducted

Answer 13

contingency table of genotypes or allele table (preferred)
Test: chi squared to show whether distribution of genotypes/alleles same in case and control. Significant result=SNP influences risk of disease

Question 14

How to calculate odds ratio

Answer 14

ref. notes. AD/BC

Question 15

How does risk differ between Mendelian disease and polygenic disease

Answer 15

mendelian=absolute risk, penetrance=probability of developing disease is high
polygenic=relative risk. odds ratio compare disease risk for different genotypes. each variant only small risk and needs to be combined with other genes contributing (cumulative) so can’t give absolute risk

Question 16

What kind of factors is coronary artery disease affected by

Answer 16

genetics: polygenic risk scores, summed genetic risk across 52 variants associated with
healthy lifestyle: no current smoking, no obesity, healthy diet, physical activity at least once weekly