Poster Presentation 9th GeneMappers Conference 2012

Skin Ageing GWAS: Peeling back the layers (#117)

Matthew H Law 1 , Sarah E Medland 1 , Gu Zhu 1 , Sri Niranjan Shekar 2 , David L Duffy 1 , Grant W Montgomery 1 , Richard A Sturm 3 , Adèle C Green 1 , Nicholas G Martin 1 , Stuart Macgregor 1
  1. Queensland Institute of Medical Research, Brisbane, QLD, Australia
  2. LSE Health and Social Care, London School of Economics, London, UK
  3. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia

Deterioration in the fine lines on the skin has been associated with solar keratoses and skin cancer. Previously we have reported that at age 12 additive gene effects explain 86% of the variation skin patterning as assessed by the six-point Beagley-Gibson scale. Heritability estimates decrease with age with non-additive gene effects explaining 62% of the variation in adults. Here, we present results of a genome-wide association study (GWAS) of skin pattern in 2550 adolescent twins and siblings from 1063 families. Two single nucleotide variants reached genome wide significance, on in the Melanocortin Receptor 1 gene (MC1R) on chromosome 16 with a p = 3.98 x 10-8. A number of functional alleles are known to exist in MC1R which strongly influence the chance of red hair and pale pigmentation; together these MC1R red hair alleles explain 4.23% of skin pattern variance. A SNP in interferon regulatory factor 4 gene (IRF4) on chromosome 6 achieved a GWAS p=2.95 x 10-8 and explains 1.53% of skin pattern variance. Red hair alleles in MC1R were also significantly associated with the number of sunburns and with sun-protective behaviours, providing evidence that genetic variants may interact with a complex trait by modulating environmental exposure.

It is reasonable to assume that a proportion of the near genome-wide significant SNPs resulting from a GWAS are associated with the studied trait, and fail to reach significance due to lower effect size or chance. For example an additional locus on chromosome 4 is of interest since includes the epidermal growth factor gene EGF (GWAS p= 2 x 10-6 1.14% of variance). To explore variants that were approaching genome wide significance further, we utilise gene and pathway based approaches.