Posts in Category ‘Publications

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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Sixteen new genes for reproductive behavior in humans

This work represents the first bona-fide genome-wide association study (GWAS) assessing reproductive behavior in humans, to which LIGA contributed the data from the Berlin Aging Study II. Overall, nearly 350,000 individuals were analyzed leading to the identification of 16 independent loci that are significantly associated with ‘age at first birth’ and/or ‘number of children ever born’. These identified loci harbor genes that are likely to have a role,in human reproduction and infertility. The study was published in the journal Nature Genetics.

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GxE study on inflammation and air polution in PD

Both air pollution exposure and systemic inflammation have been linked to Parkinson’s disease (PD). In this study, led by long-time LIGA collaborator Prof. Beate Ritz at UCLA in the USA, we correlated long term traffic related air pollution measures with genetic markers for inflammation. The analyses showed suggestive evidence that a combination of traffic-related air pollution and genetic variation in the IL1B gene may contribute to risk of developing PD. The results were published in the journal Environmental Research.

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First genome-wide GxE study in PD published

The LIGA team was part of a collaborative effort where we performed the first ever genome-wide gene-environment interaction (GxE) analysis of pesticide exposure and risk of Parkinson’s disease (PD). The results of this effort suggest that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene. This finding needs to be replicated in independent samples before it should be considered as established. The results were published in the journal Parkinsonism and Related Disorders.

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Announcement of MDSGene

Investigators from LIGA and the Institute of Neurogenetics today announced their upcoming launch of MDSGene, the Movement Disorders Society Genetics database. MDSGene aims to provide a comprehensive, systematic overview of published data on movement disorder patients reported to carry causative gene mutations. The official launch of the resource will happen during the 20th Congress of the International Movement Disorders Society which takes place in Berlin between June 19-23. After AlzGene, ALSGene, and PDGene, MDSGene (which will become available at www.mdsgene.org) represents the fourth genetics database developed by the LIGA team. The launch announcement was published as an editorial by members of the MDSGene team in the journal Movement Disorders.

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Study on 400,000 individuals finds genes for educational attainment

This study is the second effort coordinated by the Social Science Genetics Association Consortium (SSGAC) to which LIGA contributed data from the Berlin Aging Study II. This newest analysis employed a genome-wide association study (GWAS) approach in 300,000 persons searching for genetic determinants of educational achievement, the largest-ever genetics study in the social sciences. A total of 74 loci were revealed to show genome-wide significant association with years of schooling. The identified loci were enriched for genomic regions regulating gene expression in the fetal brain. The study was published in the journal Nature.

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Three new genes identified for subjective well-being

This study was coordinated by the Social Science Genetics Association Consortium (SSGAC) of which our group is a member via contributing data from the Berlin Aging Study II. In total, our study investigated the data of nearly 300,000 individuals searching for genetic determinants of subjective well-being, depressive symptoms, and neuroticism. Using a genome-wide association study (GWAS) approach, we identified 16 signals associated with one of more of the investigated phenotypes. Pinpointed loci tended to be involved in regulating gene expression in the central nervous system and adrenal or pancreas tissues. The study was published in the journal Nature Genetics.

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