Posts in Category ‘News’

New epigenetic clock analyses in the Berlin Aging Study II

1. March 2022

As part of the Lifebrain consortium project, LIGA has recently generated genome-wide DNA methylation (DNAm) profiles in a number of independent datasets, including those from the Berlin Aging Study II (BASE-II). These DNAm data were combined into an age estimate called the “epigenetic clock”, which allows comparisons to the traditional chronologically counted age. This approach was followed in the two studies spearheaded by our BASE-II colleagues in Berlin. In the first paper (published in Frontiers of Genetics), we compared the comparability of the genome-wide DNAm clock vs. a smaller version using just 7 DNAm markers. In the second paper (published in the Journal of Gerontology), both clocks were used to assess various aging-related functional traits. However, no evidence was found for an association between the DNAm clock estimates and any of the outcome measures suggesting that the epigenetic clock is not a strong biomarker for these functional domains. From the LIGA group both Yasmine Sommerer and Lars Bertram actively contributed to these analyses.

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First EMIF-AD genome-wide association study published

22. November 2020

This month the first genome-wide association study (GWAS) to emerge from the EMIF-AD MBD project was published today in the journal Translational Psychiatry. The paper describes the results of genome-wide genetic association analyses on a total of 16 Alzheimer’s disease biomarker traits (most derived from cerebrospinal fluid) in 931 participants of the European Medical Information Framework Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD). The study was funded by the EU’s EMIF program and designed and executed by the LIGA team in conjunction with a large number of international collaborators. A preprint of the m.s. had been posted earlier on bioRxiv prior to initiating the peer-review process. The study represents a detailed first account of GWAS analyses on CSF-Aβ and -tau-related traits in the EMIF-AD MBD dataset and sets the stage for genome-wide analyses of other AD-relevant clinical outcomes ascertained in this unique dataset.

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Paper on genetic risk scores in Parkinson’s disease

1. October 2020

This month, a new paper was published assessing the genetic overlap between the occurrence of hallucinations in Parkinson’s disease and Alzheimer’s and schizophrenia. To this end, genome-wide genotyping data on two population-based cohorts was used to build so called polygenic risk scores based on previously published genome-wide association studies. Genotype data for one of these cohorts was generated by the LIGA team and contributed to this international effort led by long-standing LIGA collaborator Prof. Beate Ritz at UCLA, USA. Interestingly, the strongest genetic links were observed with markers for Alzheimer’s but less so for schizophrenia suggesting that mechanisms for hallucinations in Parkinson’s may in part be driven by the same genetic architecture that leads to cognitive decline in Alzheimer’s. The study was published in the journal Neurology Genetics with Drs. Valerija Dobricic, Lars Bertram, and Christina M. Lill as LIGA co-authors.

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First genome-wide association results in EMIF-AD now available as preprint

23. September 2019

Together with several collaborating European research teams, our group is part of the European Medical Information Framework Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MDB). Specifically, the LIGA team leads the genomics and epigenomics efforts conducted in EMIF-AD MDB dataset and now completed their first genome-wide association study (GWAS) analyses on 16 traits, including 14 measures of amyloid-beta (Aβ) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to Aβ42, our data suggest novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-Aβ38 and CSF-Aβ40 levels. In subsequent work, our team will utilize the genomics data generated in EMIF-AD MDB to perform GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset. The analyses of this very first GWAS in EMIF-AD MDB were spearheaded by LIGA researcher Shengjun Hong and are now available as pre-print on bioRxiv.

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Proteomics analyses hint to new diagnostic approaches in Alzheimer’s

6. September 2019

Today, investigators behind the European Medical Information Framework Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MDB) project published their first large-scale proteomics study. The study used the “SOMAscan” a high-throughput technology allowing to analyze up to 5,000 proteins simultaneously. In EMIF-AD MDB this was performed in a total of 881 participants split into a discovery and replication group and discovered a panel of 44 proteins which, along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both groups.  Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization analyses. From the LIGA team, which is leading all genomics and epigenomics efforts in EMIF-AD MDB, three researchers contributed (Drs. Dobricic, Hong and Bertram) in the paper that is now published in the journal Alzheimer & Dementia.

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Two new LIGA papers on the role of microRNAs in neurodegeneration

6. September 2019

Together with collaborators at Imperial College London, our team systematically searched for microRNAs that show differential expression across all published expression studies in Alzheimer’s disease (AD) and Parkinson’s disease (PD). To reach this goal the LIGA team revised an established data processing workflow for genetic association results to now accommodate gene expression studies. For both diseases we identified several microRNAs that showed highly significant differential expression in blood, cerebral spinal fluid, or brains of AD / PD patients vs. controls. Future studies need to assess the possible role of these miRNAs in pathogenesis and progression as well as their utility as biomarkers for diagnosis, progression or prediction of PD. These papers represent first results of the LIGA-led MiRNetAD project funded by the DFG. The AD study was published in the journal Alzheimer’s & Dementia, the PD study in Annals of Neurology.

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