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October 2011
ENGAGE Young Investigator

Ida Surakka
PhD student, supervisor Dr. Samuli Ripatti, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland

Ida Surakka is a PhD student in Samuli Ripatti’s group at FIMM studying genetic associations on cardiovascular disease risk factors. Ida has her background in mathematics and statistics and has been working on genome-wide association analysis and imputation for different studies . In ENGAGE, Ida is one of the leading analysts in the project studying genetic associations on circulating blood lipids (the LipidAction project) and have been involved in the statistical analyses for several other Consortium-wide joint meta-analyses on different traits. In particular, she is currently involved in the ENGAGE meta-analysis project studying genetic associations on key traits with 1000 Genomes imputed datasets.

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A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

Circulating serum lipids contribute greatly to the global health by affecting the risk for cardiovascular diseases. Serum lipid levels are partly inherited and already 95 loci affecting high- and low-density lipoprotein cholesterol, total cholesterol and triglycerides have been found. Serum lipids are also known to be affected by multiple epidemiological risk factors like body composition, lifestyle and sex. It has been hypothesized that there are loci modifying the effects between risk factors and serum lipids, but to date, only candidate gene studies for interactions have been reported. We conducted a genome-wide screen with meta-analysis approach to identify loci having interactions with epidemiological risk factors on serum lipids with over 30,000 population-based samples. When combining results from our initial datasets and 8 additional replication cohorts (maximum N = 17,102) we found a genome wide significant locus in chromosome 4p15 with a joint P-value of 4.79 × 10-9 modifying the effect of waist-to-hip ratio on total cholesterol. In the area surrounding this genetic variant there were two genes having association between the genotypes and the gene expression in adipose tissue and we also found enrichment of SNP genotype – expression associations in genes belonging to lipid metabolism related functions. This article presented the key findings from the ENGAGE-led joint project LipidAction (Gene-lifestyle interaction for lipids) co-led by Samuli Ripatti (FIMM), Yurii Aulchenko and Cornelia van Duijn (Erasmus MC). This study is the first time an interaction between a genetic loci and a risk factor has been identified in a genome-wide scan through a stringent statistical design on genome-wide significance. It may be considered as a model study for future investigations on GxE interactions.

Paper:
A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

Surakka I*, Isaacs A*, Karssen LC, Laurila PP, Middelberg RP, Tikkanen E, Ried JS, Lamina C, Mangino M, Igl W, Hottenga JJ, Lagou V, van der Harst P, Mateo Leach I, Esko T, Kutalik Z, Wainwright NW, Struchalin MV, Sarin AP, Kangas AJ, Viikari JS, Perola M, Rantanen T, Petersen AK, Soininen P, Johansson A, Soranzo N, Heath AC, Papamarkou T, Prokopenko I, Tönjes A, Kronenberg F, Döring A, Rivadeneira F, Montgomery GW, Whitfield JB, Kähönen M, Lehtimäki T, Freimer NB, Willemsen G, de Geus EJ, Palotie A, Sandhu MS, Waterworth DM, Metspalu A, Stumvoll M, Uitterlinden AG, Jula A, Navis G, Wijmenga C, Wolffenbuttel BH, Taskinen MR, Ala-Korpela M, Kaprio J, Kyvik KO, Boomsma DI, Pedersen NL, Gyllensten U, Wilson JF, Rudan I, Campbell H, Pramstaller PP, Spector TD, Witteman JC, Eriksson JG, Salomaa V, Oostra BA, Raitakari OT, Wichmann HE, Gieger C, Järvelin MR, Martin NG, Hofman A, McCarthy MI, Peltonen L, van Duijn CM, Aulchenko YS¤, Ripatti S¤; for the ENGAGE Consortium.

PLoS Genetics 2011 Oct;7(10):e1002333 (Epub 2011 Oct 20)

 

doi: 10.1371/journal.pgen.1002333

*These authors contributed equally to this work;¤These authors also contributed equally to this work.


 

 

October 2011
ENGAGE Young Investigator

Aaron Isaacs



Assistant Professor, Erasmus University Rotterdam, The Netherlands

Aaron Isaacs is an Assistant Professor of Genetic Epidemiology in Cornelia van Duijn's group at Erasmus University Rotterdam. His primary research topic is the genetic basis of traits involved in cardiovascular disease, particularly lipid levels and electrocardiographic measurements. Recently, he has become involved in a major effort to study the influence of transcription and methylation on those phenotypes. In addition to his involvement with the previous ENGAGE lipid analysis, and ENGAGE's subsequent participation in the Global Lipids Genetics Consortium, Aaron was a lead analyst on the recently published project which sought to determine the influence of factors which might modify the action of genetic determinants on lipid levels (LipidAction). Currently, he is working on the analysis of lipid traits for the ENGAGE 1000 Genomes project.