Timing really is everything, shows Diana Cousminer's dissertation

M.Sc. Diana Cousminer’s thesis work entitled "The Genetics of Pubertal Growth and Timing" will be publicly examined tomorrow, on the 17th of April. The main aim of her work was to identify genetic variants influencing pubertal growth and development in both sexes. Pubertal development is a highly variable and highly heritable phenomenon. It also has major health implications since variation in pubertal growth and timing correlates with altered risk for many diseases in adulthood.

Diana Cousminer has done her thesis work at FIMM under the supervision of Academy Research Fellow Elisabeth Widén, M.D., PhD. Diana graduated from the University of Helsinki in 2010, majoring in genetics. She did her master’s thesis work in Dr. Widén’s group and then continued with the Ph.D. project. The thesis work consists of four publications, three of which have already been published in high-quality genetic journals.

In her thesis project, both Finnish families with an extreme delay in normal pubertal timing, Finnish population-based samples and several large cohorts of European origin comprising nearly twenty-thousand individuals were studied.

-While normal variation in age at menarche has been investigated in large-scale genome-wide association studies, the genetic regulation of male puberty remains less understood since the genetics of pubertal development has not been studied as heavily in boys, explains Diana.

The most important reason why male puberty is understudied is the fact that there is no easy-to-assess marker similar to menarche in boys. Diana’s work showed that simple measurements of the pubertal growth spurt could be successfully applied in gene mapping studies for detecting variants in both boys and girls, and also targeted sexual development in both sexes using data on the Tanner Pubertal Development Scale.

In the thesis work, several large-scale genome-wide association studies were performed. Altogether Diana was able to identify 11 common genetic variants that associate with pubertal development. The gene showing the strongest association is called LIN28B. Diana showed that this genetic region, earlier identified to be a menarche locus, contains variants that regulate postnatal growth and have a strong influence on growth during puberty as well as pubertal timing in both sexes. LIN28B is also an example of a link between puberty and adult health:  it is important for normal developmental timing, but associates with cancer risk and progression if it becomes dysregulated later in life.

-Another interesting finding is that while the leading association signals seem to vary between the sexes, a significant part of the genetic architecture underlying the onset of puberty is shared between males and females. Thus there is likely a substantial overlap between molecular mechanisms that regulate pubertal initiation in males and females, Diana continues.

-Coordinating large consortium studies has taught me to have a lot of patience, but I have also enjoyed the benefits of networking. I have spent the past few years in Canada. Luckily, the nature of my research, and my supervisor, has allowed me to finish my work without physically being here at FIMM.

Diana Cousminer will defend her doctoral dissertation entitled "The Genetics of Pubertal Growth and Timing" in the Faculty of Medicine, University of Helsinki, on 17 April 2015 at 13:00. The public examination will take place at Biomedicum Helsinki 1, Lecture Hall 3, Haartmaninkatu 8. Professor Gregory Gibson, Georgia Institute of Technology, will serve as the opponent, and Professor Samuli Ripatti as the custos.

The dissertation is also available in electronic form through the E-thesis service.