Molecular epidemiology studies of aging and aging-related diseases

The overall aim of my research, in the newly coined field of geroscience, is to examine the biological mechanisms underlying aging and how that contributes to increased susceptibility to certain diseases.

Project leader

Assistant professor

Sara Hägg

Phone: +46-(0)8-524 822 36

Towards this aim, I use several longitudinal studies of aging, mostly from the Swedish Twin Registry (STR), where we have multiple measurements of telomere length, DNA methylation, lipids, anthropometrics and cognitive function available among others. In addition, large-scale GWAS data and publicly available cohorts are used to increase power in studies and to assess causality using Mendelian Randomization (MR) designs.

Specific aims and projects include:

Leukocyte telomere length in aging diseases – causality and longitudinal telomere shortening

Telomeres are short DNA sequences located at the end of the chromosomes, and in each cell replication, the telomeres are shortened by approximately 20 base pairs. As a consequence, telomere shortening progress over time, and accelerated telomere attrition is seen in many aging diseases and related processes such as inflammation and oxidative stress. We have thus far been exploring longitudinal telomere shortening in the Swedish Adoption/Twin Study of Aging (SATSA) where we show that both sex and genetic risk contributes to shorter telomeres. We have also performed a series of MR studies where we investigate the causal link from having shorter telomeres on an outcome. So far we have provided evidence for causal associations with Alzheimer ’s disease, Coronary Heart Disease and to different cognitive domains. Moreover, we are currently studying associations with stress from life events, multi-morbidity and physical function.

Epigenetic influences on aging: a longitudinal genome-wide methylation study in Swedish twins at old age

The aging process is characterized by cell death and DNA modifications, and leads to gradual decline in body function and increased susceptibility to diseases. A way to study the aging process is by using epigenetics (chemical modifications on DNA) where genetic, environmental and random contributions are captured. Across life, epigenetic marks changes due to environmental pressure with dysregulation of genes, accelerated aging and disease onset as a consequence. Thus, studying these marks reflect the accumulative effects of lifestyle in relation to aging, and will increase our knowledge of the aging processes. In this project, the SATSA study is used to study longitudinal epigenetic marks of aging. To this purpose we have measured whole blood DNA methylation through the Illumina HumanMethylation450K chip repeatedly up to five times over a 20 year span in 368 twins. In addition, other biomarker data such as genotypes, telomere length, cognition, lipid levels and anthropometrics were collected. Currently, we are exploring longitudinal epigenome-wide association studies (LEWAS) of aging. We are also performing extended epigenetic analyses of the ApoE locus and associations to dementia risk, as well as using a discordant twin approach to highlight environmental contributions to diseases such as Alzheimer’s disease and Parkinson. Moreover, longitudinal analyses using the epigenetic clock – a biological age predictor using DNA methylation data – is undertaken.


Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.
Hägg S, Fall T, Ploner A, Mägi R, Fischer K, Draisma H, et al
Int J Epidemiol 2015 Apr;44(2):578-86

Age- and sex-specific causal effects of adiposity on cardiovascular risk factors.
Fall T, Hägg S, Ploner A, Mägi R, Fischer K, Draisma H, et al
Diabetes 2015 May;64(5):1841-52

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.
Horikoshi M, Mӓgi R, van de Bunt M, Surakka I, Sarin A, Mahajan A, et al
PLoS Genet. 2015 Jul;11(7):e1005230

Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models.
Chen X, Kuja-Halkola R, Rahman I, Arpegård J, Viktorin A, Karlsson R, et al
Am. J. Hum. Genet. 2015 Nov;97(5):708-14

Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity.
Hägg S, Ganna A, Van Der Laan S, Esko T, Pers T, Locke A, et al
Hum. Mol. Genet. 2015 Dec;24(23):6849-60

Telomere Length Shortening and Alzheimer Disease--A Mendelian Randomization Study.
Zhan Y, Song C, Karlsson R, Tillander A, Reynolds C, Pedersen N, et al
JAMA Neurol 2015 Oct;72(10):1202-3

The impact of low-frequency and rare variants on lipid levels.
Surakka I, Horikoshi M, Mägi R, Sarin A, Mahajan A, Lagou V, et al
Nat. Genet. 2015 Jun;47(6):589-97

DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.
Perry J, Hsu Y, Chasman D, Johnson A, Elks C, Albrecht E, et al
Hum. Mol. Genet. 2014 May;23(9):2490-7

Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break.
Lindgren E, Hägg S, Giordano F, Björkegren J, Ström L
Cell Cycle 2014 ;13(23):3645-58

Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers.
Deelen J, Beekman M, Codd V, Trompet S, Broer L, Hägg S, et al
Int J Epidemiol 2014 Jun;43(3):878-86