Heritability of retinal Heritability of retinal phenotypes in a phenotypes in a

European populationEuropean population

Tom Richart, MD, MSc Dept. of Genetic Epidemiology, UM Maastricht, NL

Laboratory of Hypertension, KU Leuven, BE

Phenotype – genotype and phenotype – biomarker associations: focusing on

arterial phenotypes, both micro- and macrovascular;

Phenotype reproducibility is crucial for proper analyses;

What is the heritability of arterial phenotypes in a general population?

What are the genetic and environmental correlations for arterial phenotypes?

Research questionsResearch questionsRetinaRetina

The retinal phenotyping technique is non-invasive, easy and has good

reproducibility;

Analyses indicate retinal vessel caliber heritability around 0.30 and are in

concordance with Beaver Dam study results;

Further analyses are planned, assessing genetic and evironmental correlations

with other vascular phenotypes.

Key pointsKey pointsRetinaRetina

Non-mydriatic retinal cameraNon-mydriatic retinal cameraRetinaRetinaRetinaRetina

Image post-processingImage post-processingRetinaRetinaRetinaRetina

Image post-processingImage post-processingRetinaRetinaRetinaRetina

A non-mydriatic approach is used, no need for dilating agents;

Digital images are processed with validated software (ARIC study);

Resulting phenotypes are:

Central retinal arteriole (CRAE) and venule (CRVE) equivalents

Arteriole-to-venule ratios (AVR)

Phenotyping techniquePhenotyping techniqueRetinaRetina

We assessed intra- and inter-observer reproducibility (100 readings);

Intra-observer differences ≤10%; inter-observer differences ≤16%;

Differences were due to randomness, no associations were found with

participant characteristics (age, sex, BP, treatment for hypertension).

ReproducibilityReproducibilityRetinaRetina

Reproducibility of AVRReproducibility of AVRRetinaRetina

observer 1

0.6 0.7 0.8 0.9 1.0

-0.2

-0.1

0.0

0.1

0.2

1st

- 2n

d R

ead

ing

observer 2

0.6 0.7 0.8 0.9 1.0

-0.2

-0.1

0.0

0.1

0.2

1st

- 2n

d R

ead

ing

inter-observer

0.6 0.7 0.8 0.9 1.0

-0.2

-0.1

0.0

0.1

0.2

1st

- 2n

d O

bse

rver

SAGE software; ASSOC program;

Models considered:

Unadjusted;

Adjusted for sex, age, BP, BMI and antihypertensive drugs.

Heritability: methodsHeritability: methodsRetinaRetina

167 pedigree members with complete information; 24 singletons with complete

information;

Age 46.7±7.6; 50.3% women;

Pedigrees are rather small, adding more observations is necessary to make

results more reliable.

Heretability: population characteristicsHeretability: population characteristicsRetinaRetina

HeritabilityHeritability

Characteristic Unadjusted Fully adjusted

CRAE (PH) 0.33* -

CRVE (PH) 0.18* -

AVR (PH) 0.35* -

ACCORD/BPACCORD/BPVitamin DVitamin DRetinaRetina

* p<0.001

The retinal phenotyping technique is non-invasive, easy and has good

reproducibility;

Analyses indicate retinal vessel caliber heritability around 0.30 and are in

concordance with Beaver Dam study results;

Further analyses are planned, assessing genetic and evironmental correlations

with other vascular phenotypes.

Key pointsKey pointsRetinaRetina