Lipid-Associated Variants near ANGPTL3 and LPL Show Parent-of-Origin Specific Effects on Blood Lipid Levels and Obesity.

Anna Lessmark,Tiinamaija Tuomi,Emma Ahlqvist,Marta Vitai,Gad Hatem,Laszlo Koranyi,Rashmi B Prasad,Leif Groop,Györgyi Kovacs

doi:10.3390/genes13010091

Abstract

Parent-of-origin effects (POE) and sex-specific parental effects have been reported for plasma lipid levels, and a strong relationship exists between dyslipidemia and obesity. We aim to explore whether genetic variants previously reported to have an association to lipid traits also show POE on blood lipid levels and obesity. Families from the Botnia cohort and the Hungarian Transdanubian Biobank (HTB) were genotyped for 12 SNPs, parental origin of alleles were inferred, and generalized estimating equations were modeled to assess parental-specific associations with lipid traits and obesity. POE were observed for the variants at the TMEM57, DOCK7/ANGPTL3, LPL, and APOA on lipid traits, the latter replicated in HTB. Sex-specific parental effects were also observed; variants at ANGPTL3/DOCK7 showed POE on lipid traits and obesity in daughters only, while those at LPL and TMEM57 showed POE on lipid traits in sons. Variants at LPL and DOCK7/ANGPTL3 showed POE on obesity-related traits in Botnia and HTB, and POE effects on obesity were seen to a higher degree in daughters. This highlights the need to include analysis of POEs in genetic studies of complex traits.

Highlights

Genomics, Diabetes and Endocrinology, Department of Clinical Sciences, Lund University, CRC, Abdominal Center, Endocrinology, Helsinki University Central Hospital, Research Program for Clinical and Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290 Helsinki, Finland
To determine the genetic basis of these parental effects, locus-by-locus paternal, maternal, and parent-of-origin effects on plasma lipid levels were assessed for the selected loci in the discovery and replication sub-cohorts of the Botnia study
Sex-specific parental effects of plasma lipid levels have been reported in multiple family studies, with the lipid levels showing a certain degree of heritability in the families

Summary

Introduction

Parent-of-origin effects (POE) and sex-specific parental effects have been reported for plasma lipid levels, and a strong relationship exists between dyslipidemia and obesity. Sex-specific parental effects were observed; variants at ANGPTL3/DOCK7 showed POE on lipid traits and obesity in daughters only, while those at LPL and TMEM57 showed POE on lipid traits in sons. Variants at LPL and DOCK7/ANGPTL3 showed POE on obesity-related traits in Botnia and HTB, and POE effects on obesity were seen to a higher degree in daughters. This highlights the need to include analysis of POEs in genetic studies of complex traits. There is a strong genetic component, and >350 SNPs corresponding to

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