Abstract

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POE) in genome-wide genotype data of unrelated individuals.

The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ~4,000 trios).

Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta=0.11 (SD), P<0.0027) compared to the respective maternal alleles.

Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.

Assistant Professor Zoltan Kutalik

Zoltán trained as applied mathematician (specialized in statistics) and graduated in 2002 in Hungary. He obtained his MPhil degree in 2003 at the University of Manchester (UK) and his PhD in 2006 at the University of East Anglia, Norwich, UK. His PhD research aimed at modelling and connecting bacterial growth at the population-, single cell- and genetic levels.

2006-2012 Zoltán was a post-doctoral research assistant, then junior lecturer at the Department of Medical Genetics of the University of Lausanne (Switzerland) and affiliated with the Swiss Institute of Bioinformatics. In 2013 he became an Assistant Professor at the Institute of Social and Preventive Medicine (IUMSP) of the Lausanne University Hospital (Switzerland).

His main interest lies in developing statistical methods that connect large scale data sets (SNPs, gene expression, clinical phenotypes) in the context of genetic association studies.