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Waldenberger, MelanieORCID iD iconorcid.org/0000-0003-0583-5093
Publications (2 of 2) Show all publications
Perry, J. R. B., Hsu, Y.-H., Chasman, D. I., Johnson, A. D., Elks, C., Albrecht, E., . . . Murray, A. (2014). DNA mismatch repair gene MSH6 implicated in determining age at natural menopause. Human Molecular Genetics, 23(9), 2490-2497
Open this publication in new window or tab >>DNA mismatch repair gene MSH6 implicated in determining age at natural menopause
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2014 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, no 9, p. 2490-2497Article in journal (Refereed) Published
Abstract [en]

The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to 50 of the variation in both age at menarche and menopause, but to date the known genes explain 15 of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P 1.9 10(9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-224998 (URN)10.1093/hmg/ddt620 (DOI)000334359100022 ()
Available from: 2014-05-26 Created: 2014-05-26 Last updated: 2017-12-05Bibliographically approved
Albrecht, E., Sillanpaa, E., Karrasch, S., Alves, A. C., Codd, V., Hovatta, I., . . . Schulz, H. (2014). Telomere length in circulating leukocytes is associated with lung function and disease. European Respiratory Journal, 43(4), 983-992
Open this publication in new window or tab >>Telomere length in circulating leukocytes is associated with lung function and disease
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2014 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 43, no 4, p. 983-992Article in journal (Refereed) Published
Abstract [en]

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-224752 (URN)10.1183/09031936.00046213 (DOI)000334261900013 ()
Available from: 2014-05-20 Created: 2014-05-19 Last updated: 2017-12-05Bibliographically approved
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0583-5093

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