Whole-genome evaluation of complex traits using SNP, haplotype, or QTL

information

Gorjanc G. & Hickey J. M.

Genetika 2012, Maribor, Slovenia

Introduction

• Whole-genome technologies rich data

• In complex traits (e.g., body height, weight, …) gene discovery still very limited

• Rich genome-wide data can be used for prediction (classicaly based on phenotype and pedigree data)

• AIM: Show the value of different types of information for prediction in complex traits

Different sources of information (simplistic scheme)

k-1 k k+1 k+2 k+3 k+4 k+5 k+6

… C C T A G A … … G G A T C T … … C C T A G A … … G G A T C T …

… C C T A G A … … G G A T C T … … C T C A G A … … G A G T C T …

… C T C A T A … … G A G T A T … … C T C A T A … … G A G T A T …

+0 cm

+1 cm

+2 cm

QTL SNP SNP

Haplotypes

Methods - Idea

Methods - Simulation

AGV

Methods – Simulated data

1

Genotype

Pedigree

Phenotype

Genotype

2

3

4

5

6

7

8

9

10

Genotype

Genotype

Validation Calibration Gen.

Methods – Statistical analysis

GWAS vs. relationship modelling

• GWAS

• Relationships use the same underlying information (phenotype and genotype data) to infer the sum of all GWAS estimates

Haplotype similarity

• Long haplotypes „explosion“ in #haplotypes

• But parts of haplotypes are similar efective number of haplotypes is smaller

• Similarities (several variations tested)

k-1 k k+1 k+2 k+3 k+4 k+5 k+6

… C C T A G A … … G G A T C T … … C T C A G A … … G A G T C T … … C T C A T A … … G A G T A T …

Haplotype 1 Haplotype 2 Haplotype 3

Haplotype 1 6/6 4/6 3/6

Haplotype 2 6/6 5/6

Haplotype 3 6/6

Results – Gaussian QTL

QTL Pedigree SNP V SNP Y

Haplotypes – no similarity

Haplotypes – similarity 1 Haplotypes – similarity 2

QTL

Results – Gamma QTL

QTL Pedigree SNP V SNP Y

Haplotypes – no similarity

Haplotypes – similarity 1 Haplotypes – similarity 2

QTL

Conclusions

• Genome-wide information increases accuracy in comparison to classic methods using pedigrees and phenotypes only

• Long haplotypes large #haplotypes – low accuracies

– similarities help

– no advantage over SNP data (perhaps due to large #haplotypes)

• Accuracies drop in further generations (not so much with Gamma QTL data)

can not predict distant relatives or unrelated individuals accurately!!!

• Even with QTL data accuracies are not perfect!!!

Whole-genome evaluation of complex traits using SNP, haplotype, or QTL

information

Gorjanc G. & Hickey J. M.

Genetika 2012, Maribor, Slovenia