Cardiovascular diseases account for 30-40% of deaths in Western countries. Obesity and dyslipidemias, mainly elevated cholesterol and triglycerides, are well-established risk factors for cardiovascular diseases. However, these factors explain only a relatively small fraction of the individual disease risk.
The main aim of Licentiate of Medicine Joel Rämö’s thesis entitled “Genomic, metabolic and clinical profiling of dyslipidemias in families”, to be publicly examined tomorrow, November 6th, was to identify risk factors for cardiovascular diseases beyond these traditional measures. The impact of family history and presence of fatty liver were of special interest to this work.
Joel graduated from the Faculty of Medicine of the University of Helsinki in 2018. Thanks to the faculty’s MD-PhD rotation programme, he had a chance to work in different labs as a summer student throughout his studies. The rotation he did in 2013 in Aarno Palotie’s and Samuli Ripatti’s labs at FIMM raised his scientific curiosity and led into starting a PhD project under the supervision of Aarno, Samuli and Kirsi Pietiläinen.
Joel feels that FIMM has provided an excellent research environment for him.
FIMM is a great place to do science. It's the most collaborative and closely knit of all research communities I've been part of in Helsinki. Its scope, too, is quite unique.
Joel’s thesis consists of three publications, all of which have already been published in high-quality journals. For his thesis, he has used several different, complementary approaches and study settings, including twin studies and hyperlipidemic families.
In the first sub-study, Joel studied the impact of fatty liver by quantifying circulating metabolites during an oral glucose tolerance test in monozygotic twin pairs discordant for BMI. The results showed that the twins who were also discordant for liver fat differed across a wide range of metabolites, many of which might be relevant for the development of atherosclerosis.
In the other two sub-studies, Joel focused on familial hyperlipidemias. First, he studied familial combined hyperlipidemia, which is typically characterized by elevated total cholesterol or triglycerides. He was able to show that only a small fraction of the familial patients had rare APOE or APOA5 mutations that could explain their dyslipidemia. On the other hand, almost a third of the affected family members had clearly elevated polygenic burden.
Next, Joel compared cardiovascular disease risk and lipidomic profiles between familial hyperlipidemia cases and individuals with a similar hyperlipidemia but no known family history. The conclusion was that the familial cases share similar and overlapping pathophysiology with common population-ascertained hyperlipidemias, and do not seem to confer differential cardiovascular disease risk.
Together with Pietari Ripatti, we found that familial combined hyperlipidemia, previously thought to be monogenic, seems to be largely polygenic. Our data suggest limited clinical utility for genetic screens for these patients and, on a personal level, it has changed the way that I approach familial dyslipidemias in the clinic.
The fact that Joel has been able to complete his theses while finishing his medical studies and working in the clinic is definitely worth acknowledging. Outside the work Joel relaxes with her favorite hobbies – sports and traveling.
In the summer, I play soccer, cycle and run on trails in the central park. In the winter, I try to squeeze in floorball and gym and dream of warmer times. Travelling is one fix for solar malalignment, as is getting a pair of properly fitted skis.
Joel plans to specialize within medicine. He would love to work in a university setting, researching the same patients that he sees in the clinic.
For the time being, improving as a generalist is rewarding, but I foresee myself focusing on a narrower subfield in the future. I don't want to decide too early, though. If anything, I've learned that interests are liable to change as one explores new topics.
The public examination of Joel Rämö’s doctoral dissertation will take place on 6 November at 12 o'clock noon in Lecture Hall 1 at Haartman Institute, Haartmaninkatu 3 with the permission of the Faculty of Medicine of the University of Helsinki. Professor Katriina Aalto-Setälä (University of Tampere) will serve as the opponent and Professor Samuli Ripatti as the custos. The dissertation is also available in an electronic form.