News

Proteomics analyses hint to new diagnostic approaches in Alzheimer’s

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

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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GWAS on educational attainment in more than 1 million individuals

A new genome-wide association study (GWAS) investigated the genetics of educational attainment in over 1 million individuals, including 2,000 from the Berlin Aging Study II (BASE-II) contributed by our group. The study represents one of the largest GWAS ever performed to date and identified nearly 1,300 independent lead SNPs to show genome-wide significant association with education. Many of the identified variants are located in genes involved in brain-development processes and neuron-to-neuron communication. Polygenic analyses suggest that up to 13% of the variance underlying inter-individual differences in educational attainment can now be explained by these data, more than explained by household income but less than by parental educational attainment. The study was published in the journal Nature Genetics.

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First ever field synopsis of genetic association studies in dystonia

Researchers from LIGA together with two colleagues from the Institute of Neurogenetics this month published the first ever field synopsis for genetic association studies in dystonia. The study, led by LIGA PhD student Olena Ohlei, aimed at separating the wheat from the chaff for genetic association results in datasets of isolated dystonia. To this end, we scrutinized more than 3,500 published articles resulting in the inclusion of 42 independent publications allowing 134 meta-analyses on 45 variants across 17 genes. While subsequently performed meta-analyses pinpointed several association signals with variants in TOR1A, DRD1, and ARSG, no single variant displayed compelling association with dystonia in the available data highlighting the need for additional large-scale studies. The publication was part of an ongoing DFG-funded project led by Lars Bertram and Jeanette Erdmann at the Institute of Cardiogenetics. The Ohlei et al paper is now published in the Journal Parkinsonism and Related Disorders (after having been posted on bioRxiv prior to peer-review).

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Genome-wide study pinpoints 148 loci for cognitive function

Much like many other human phenotypes, cognitive function is a highly polygenic trait. In the largest genome-wide association study (GWAS) performed to date, our colleagues Gail Davies and Ian Deary at University of Edinburgh spearheaded analyses on over 300,000 individuals (including ~2000 from the Berlin Aging Study II, co-led by LIGA investigators) identifying nearly 150 independent genetic loci associated with cognitive function, many of which had not been known previously. Within the novel genetic loci are DNA variants associated with neurodevelopmental and neurodegenerative disorders (such as Alzheimer’s and Parkinson’s diesease), physical and psychiatric illnesses, and brain structure. The results of this study shed important new light on the inborn factors contributing to cognitive (dys-)function in humans. The study was published in the journal Nature Communications.

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Systematic meta-analyses identify differentially expressed microRNAs in Parkinson’s disease

The aim of this study was to identify microRNAs that show consistent differential expression across all published expression studies in Parkinson’s disease (PD). To this end, we performed a systematic literature search on microRNA expression studies in PD and meta-analyzed the extracted data. We identified several microRNAs that showed highly significant differential expression in PD blood and brain. Future studies need to assess the possible role of these miRNAs in PD pathogenesis and progression as well as the utility as biomarkers for diagnosis, progression or prediction of PD. The study was published as pre-print on bioRxiv.

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New genes identified for human longevity

Elucidating factors that influence human longevity is of great interest to a number of disciplines in medicine and biology. In this study, LIGA contributed genome-wide data from the Berlin Aging Study II to a meta-analysis using parental life span in >600000 individuals as outcome measure. We identified associations at HLA-DQA/DRB1 and LPA and found that genetic variants that increase educational attainment positively affects lifespan whereas increasing BMI showed negative effects. The study was published in the journal Nature Communications.

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