Ida Surakka’s dissertation shows the power of large cohort studies in identifying genetic determinants of lipid levels
Cardiovascular diseases are the most common cause of death worldwide and circulating blood lipids such as cholesterol and triglycerides are well-established risk factors for cardiovascular diseases. Genetic factors are known to explain approximately half of the observed high inter-individual lipid level variability.
The main aim of Ida Surakka’s thesis, to be publically examined tomorrow, November 7th, was to identify genetic markers and biological pathways behind circulating blood lipid levels. M.Sc. Ida Surakka is a Ph.D. student at FIMM and in Hjelt Institute, Faculty of Medicine, University of Helsinki. In her thesis project, several large cohorts of European origin comprising tens of thousands of individuals were studied. Based on this work, almost a hundred genetic loci associated with lipid levels were identified using large-scale genome-wide approaches. Her dissertation, entitled “Genetics of Circulating Blood Lipids”, was supervised by Professor Samuli Ripatti.
Getting to grips with lipid genetics
Ida’s thesis consists of four publications three of which have already been published in high-quality journals. In 2008, soon after she started her PhD project, she was already a part of the team reporting the results of the first genome-wide association analysis of lipid levels based on 16 European cohorts. This groundbreaking work led to a publication in Nature Genetics, the highest-impact journal in the field of Genetics. In all the rest of the thesis publications she has been the person responsible for coordinating the collaboration, data harmonization and analyses.
In the second study the research group concentrated on searching gene-environment interactions on lipids. They were able to show that a certain genetic marker modifies the effect of waist-to-hip-ratio on total cholesterol levels. This was the first reported genome-wide significant gene-environment interaction for lipid levels.
Imputation is a method where missing genotype information is statistically inferred based on available reference sets. In the third study of her thesis Ida aimed to develop better imputation strategies for founder populations, concentrating on the Finnish population. She was able to show that population specific reference panels improved the imputation quality significantly for both common and rare variants. This knowledge was utilized in the last publication of her thesis. In this huge study, nearly 10 M genetic markers and more than 60.000 individuals were studied and ten new genetic associations to lipids identified. Furthermore, a new lead marker was identified for almost all of the previously identified 83 loci.
Big is beautiful
Ida’s thesis work has significance beyond the lipid level genetics since it also increases our knowledge on studying complex traits in general.
-To me, the most important part of this thesis is the last paper where we specifically aimed to screen for low-frequency variants affecting lipid levels. Some of these high-impact variants may well later lead to next generation cholesterol medication. If effective co-operation and modern methodology made our study successful I see no reason why this would not work for other complex traits as well, Ida commented.
-We have learned that what actually matters most is the scale of the study, both in terms of individuals and genomic data. Lipid levels are widely used in clinical practice and are simple traits to measure and thus large cohorts have been available. By utilizing these cohorts and the imputation strategy we are now starting to get close to understanding almost half of the heritability.
The carrot works a lot better than the stick
Ida has studied statistics, especially biometry, in the Faculty of Science in the University of Helsinki. She graduated in 2011 but started her PhD work well before that as the first student of Samuli Ripatti.
-Luckily, I am both a systematic and a diplomatic person by nature. These have been very valuable features in coordinating the large consortium projects. It soon became clear to me that when I need some data it is much more efficient to use the carrot, not the stick – count to ten and write a new polite message.
Outside the work Ida relaxes with her favorite hobbies – knitting and other needlework. She is also a great nature lover and spends much of her free-time hiking in the nearby forests.
Ida’s near future plans contain more work with the lipids but this time in Academy Professor Jaakko Kaprio’s group. She hopes to be able to find more functional variants associating with lipid levels especially in the Finnish population.
The public examination of M.Sc. Ida Surakka’s doctoral dissertation, Genetics of Circulating Blood Lipids, will take place on 7th November 2014 at 12 o´clock in the lecture hall 1, Kytösuontie 9. The opponent is Prof. Tarja Laitinen (Department of Pulmonary Diseases and Clinical Allergology,Turku University Hospital and University of Turku) and the custos Professor Samuli Ripatti.