2012 © Institute for Molecular Medicine Finland FIMM
Genes influencing puberty and their impact on adult health
Academy Research Fellow Elisabeth Widén, MD, PhD
Complex interactions between genes and environmental factors contribute to the lifetime risk for common, non-communicable disease. Yet, most of the underlying disease genes and mechanisms remain poorly understood. Based on epidemiological studies it appears that the disease risk correlates with distinct patterns of fetal and childhood growth. Puberty is an example of such an event. It is strongly regulated by genes and its early timing is associated with increased risk for several adult health outcomes, e.g. obesity, type 2 diabetes and hormone dependent cancers, but the underlying mechanisms behind this link remain unknown. Given the association between puberty and adult health we hypothesize that the same genes and genetic pathways may regulate both pubertal growth and maturation and its associated adult health outcomes.
The overall aim of our research is to identify genes influencing puberty and to evaluate their impact on adult health. To obtain comparable data from both females and males, the main strategy is to map a manifestation of puberty that is similar between sexes, i.e. the pubertal height growth spurt. To achieve our goal, we utilize large population cohorts with longitudinal growth data in addition to genome-wide mapping and sequencing technologies. In collaboration with others, we have also carried out gene mapping of other aspects of childhood growth and maturation.
Studying Finnish cohorts with longitudinal height data we identified significant association between the timing of the pubertal growth spurt and variants nearby the gene LIN28B (Widén et al., 2010). We further demonstrated that distinct variants in the LIN28B-region affect both prepubertal and pubertal growth in a complex and sex-specific manner Our current work includes meta-analysis of multiple aspects of pubertal growth in extended population cohorts of European descent and mapping rare genetic variants influencing the normal extreme of pubertal timing. We will evaluate the impact of the identified puberty genes on adult health in collaboration with clinicians and by studying the population resources available at the National Institute for Health and Welfare.
We envision that our project will uncover new knowledge on molecular mechanisms influencing development and growth. In addition we anticipate the project to elucidate critical pathways modifying adult disease risk, thereby potentially providing novel prospects for improved prevention and intervention strategies.
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Selected Publications
- Widén E, Ripatti S, Cousminer DL, Surakka I, Lappalainen T, Jarvelin MR, Eriksson JG, Raitakari O, Salomaa V, Sovio U, Hartikainen AL, Pouta A, McCarthy MI, Osmond C, Kajantie E, Lehtimaki T, Viikari J, Kahonen M, Tyler-Smith C, Freimer N, Hirschhorn JN, Peltonen L, Palotie A. Distinct variants at LIN28B influence growth in height from birth to adulthood Am J Hum Genet 2010;86:773-782
- Freathy RM, Sovio U, Mook-Kanamori DO, Prokopenko I, Timpson NJ, Berry DJ, Warrington NM, Widén E, Hottenga JJ, Kaakinen M, Lange LA, Bradfield JP, Kerkhof M, Marsh JA, Magi R, 7, Chen C-M, Adair LS, Aulchenko YS, Bennett AJ, Borja JB, Bouatia-Naji N, Charoen P, Coin LJM, Cousminer DL, de Geus E, Deloukas P, Elliott P, Evans D, Froguel P, Glaser B, Groves CJ, Hartikainen A-L, Hassanali N, Hofman A, Holly JMP, Hypponen E, Kanoni S, Knight BA, Laitinen J, Lindgren CM, O'Reilly P, Pennell PE, Postma DS, Pouta A, Ramasamy A, Rayner NW, Ring SM, Rivadeneira F, Shields BM, Strachan DP, Surakka I, TaanilaA, Tiesler C, Uitterlinden AG, van Duijn CM , Wijga AH, Willemsen G, Zhao ZHJ38, Steegers EAP, Hattersley AT, Eriksson JG, Peltonen L, Mohlke KL, Grant SFA, 38, 42, Hakonarson H, Koppelman GH, Dedoussis GV, Heinrich J, Palmer LJ, Frayling TM, Boomsma D, Davey Smith8 G, Power C, Jarvelin M-R, Jaddoe VWV, McCarthy MI. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nature Genet. 2010; 42: 430-435
- Elks CE, Perry JR, Sulem P, Chasman DI, Franceschini N, He C, Lunetta KL, Visser JA, Byrne EM, Cousminer DL, Gudbjartsson DF, Esko T, Feenstra B, Hottenga JJ, Koller DL, Kutalik Z, Lin P, Mangino M, Marongiu M, McArdle PF, Smith AV, Stolk L, van Wingerden SH, Zhao JH, Albrecht E, Corre T, Ingelsson E, Hayward C, Magnusson PK, Smith EN, Ulivi S, Warrington NM, Zgaga L, Alavere H, Amin N, Aspelund T, Bandinelli S, Barroso I, Berenson GS, Bergmann S, Blackburn H, Boerwinkle E, Buring JE, Busonero F, Campbell H, Chanock SJ, Chen W, Cornelis MC, Couper D, Coviello AD, d'Adamo P, de Faire U, de Geus EJ, Deloukas P, Doring A, Smith GD, Easton DF, Eiriksdottir G, Emilsson V, Eriksson J, Ferrucci L, Folsom AR, Foroud T, Garcia M, Gasparini P, Geller F, Gieger C, Consortium TG, Gudnason V, Hall P, Hankinson SE, Ferreli L, Heath AC, Hernandez DG, Hofman A, Hu FB, Illig T, Jarvelin MR, Johnson AD, Karasik D, Khaw KT, Kiel DP, Kilpelainen TO, Kolcic I, Kraft P, Launer LJ, Laven JS, Li S, Liu J, Levy D, Martin NG, McArdle WL, Melbye M, Mooser V, Murray JC, Murray SS, Nalls MA, Navarro P, Nelis M, Ness AR, Northstone K, Oostra BA, Peacock M, Palmer LJ, Palotie A, Pare G, Parker AN, Pedersen NL, Peltonen L, Pennell CE, Pharoah P, Polasek O, Plump AS, Pouta A, Porcu E, Rafnar T, Rice JP, Ring SM, Rivadeneira F, Rudan I, Sala C, Salomaa V, Sanna S, Schlessinger D, Schork NJ, Scuteri A, Segre AV, Shuldiner AR, Soranzo N, Sovio U, Srinivasan SR, Strachan DP, Tammesoo ML, Tikkanen E, Toniolo D, Tsui K, Tryggvadottir L, Tyrer J, Uda M, van Dam RM, van Meurs JB, Vollenweider P, Waeber G, Wareham NJ, Waterworth DM, Weedon MN, Wichmann HE, Willemsen G, Wilson JF, Wright AF, Young L, Zhai G, Zhuang WV, Bierut LJ, Boomsma DI, Boyd HA, Crisponi L, Demerath EW, van Duijn CM, Econs MJ, Harris TB, Hunter DJ, Loos RJ, Metspalu A, Montgomery GW, Ridker PM, Spector TD, Streeten EA, Stefansson K, Thorsteinsdottir U, Uitterlinden AG, Widén E, Murabito JM, Ong KK, Murray A. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nat Genet. 2010;42:1077-1085