• In English
• Suomeksi

2009 © Institute for Molecular Medicine Finland FIMM

Widén Group

Academy Research Fellow Elisabeth Widén, MD, PhD

The main focus of the research group is the genetic regulation of pubertal growth and maturation. Most mammals undergo puberty as their postnatal growth is tailing off, but in humans puberty is accompanied by a growth spurt during which the final adult stature and body proportions are attained. The pubertal growth spurt, which is tightly correlated with pubertal sexual maturation, accounts for as much as 15—20 % of final stature and is characterized by a large variation of tempo and timing, both within and between the sexes. Genes and environmental factors contribute to the variation in pubertal growth and maturation, but twin studies indicate that a substantial proportion of the variance is under genetic control.

Little is yet known about the genetic framework regulating puberty. A downward secular trend in the timing of puberty has been apparent during the last century, which potentially might constitute a major public health concern, since early pubertal maturation is associated with long-term adverse health effects, such as increased risk of e.g. obesity and hormone-dependent cancers. We hypothesize that disentangling the genetic architecture controlling the onset of puberty significantly could improve the understanding of the complex interplay of molecular factors regulating pubertal growth and maturation in general, which in turn also might elucidate the mechanisms advancing the onset of puberty.

Our primary aim is to map and characterize genes regulating pubertal growth. To achieve this goal we are conducting both genome-wide mapping studies in population based cohorts, but also have performed genome-wide linkage mapping of genes co-segregating with constitutional delay of pubertal growth and maturation in multiply affected families. Our previous studies of constitutional pubertal delay show that the trait often segregates in an autosomal dominant fashion and we have successfully mapped a gene on chromosome 2 co-segregating with delayed puberty in extended families. The ongoing research activities during 2009 include the genome-wide association mapping of a gene region influencing pubertal growth in the Finnish population. In this study we were able to further identify the presence of two independent genetic effects in the gene region both exerting broad, complex and sex-specific influences on the complete postnatal growth trajectory. In addition we also are involved in ongoing international

collaborations on e.g. the genetic mapping of childhood growth related traits and age of menarche. In addition we have pursued the fine-mapping of the gene on chromosome 2, co-segregating with delayed pubertal onset.  The results of the research activities of year 2009 are still unpublished, but have so far been summarized in 2 papers under review.

Selected Publications:

Wehkalampi K, Widén E, Laine T, Palotie A, Dunkel L. Patterns of Inheritance of Constitutional Delay of Growth and Puberty in Families of Adolescent Girls and Boys Referred to Specialist Pediatric Care. J. Clin Endocrinol, Metab. 2008;93:723-8.

Wehkalampi K, Widén E, Palotie A, Dunkel L.  A locus of the timing of puberty with a chromosome 2 locus. J Clin Endocrinol Metab. 2008;93:4833-4839.

Sovio U, Bennett AJ, Millwood IY, Molitor J, O'Reilly PF, Timpson NJ, Kaakinen M, Laitinen J, Haukka J, Pillas D, Tzoulaki I, Molitor J, Hoggart C, Coin LJ, Whittaker J, Pouta A, Hartikainen AL, Freimer NB, Widén E, Peltonen L, Elliott P, McCarthy MI, Jarvelin MR. Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966 PLoS Genet 2009;5:e1000409.