BACKGROUND: We investigated blood DNA methylation patterns associated with 15 well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer\'s disease (AD) pathophysiology, neuroinflammation, and neurodegeneration.
METHODS: We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer\'s Disease (EMIF-AD) study using the EPIC array.
RESULTS: We identified Bonferroni-significant differential methylation associated with CSF YKL-40 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL-40 levels correlating with plasma YKL-40 levels. A co-localization analysis showed shared genetic variants underlying YKL-40 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co-methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development.
CONCLUSIONS: We conducted the most comprehensive epigenome-wide association study (EWAS) of AD-relevant CSF biomarkers to date. Future work should explore the relationship between YKL-40 genotype, DNA methylation, and protein levels in the brain.
CONCLUSIONS: Blood DNA methylation was assessed in the EMIF-AD MBD study. Epigenome-wide association studies (EWASs) were performed for 15 Alzheimer\'s disease (AD)-relevant cerebrospinal fluid (CSF) biomarker measures. Five Bonferroni-significant loci were associated with YKL-40 levels and seven with neurofilament light chain (NfL). DNA methylation in YKL-40 co-localized with previously reported genetic variation. DNA methylation potentially mediates the effect of single-nucleotide polymorphisms (SNPs) in YKL-40 on CSF protein levels.

BACKGROUND: Dementia is a multifactorial disease with Alzheimer\'s disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.
METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.
RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3).
CONCLUSIONS: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD.
CONCLUSIONS: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.

C4 photosynthesis is a complex trait requiring multiple developmental and metabolic alterations. Despite this complexity, it has independently evolved over 60 times. However, our understanding of the transition to C4 is complicated by the fact that variation in photosynthetic type is usually segregated between species that diverged a long time ago. Here, we perform a genome-wide association study (GWAS) using the grass Alloteropsis semialata, the only known species to have C3, intermediate, and C4 accessions that recently diverged. We aimed to identify genomic regions associated with the strength of the C4 cycle (measured using δ13C), and the development of C4 leaf anatomy. Genomic regions correlated with δ13C include regulators of C4 decarboxylation enzymes (RIPK), nonphotochemical quenching (SOQ1), and the development of Kranz anatomy (SCARECROW-LIKE). Regions associated with the development of C4 leaf anatomy in the intermediate individuals contain additional leaf anatomy regulators, including those responsible for vein patterning (GSL8) and meristem determinacy (GIF1). The parallel recruitment of paralogous leaf anatomy regulators between A. semialata and other C4 lineages implies the co-option of these genes is context-dependent, which likely has implications for the engineering of the C4 trait into C3 species.

Shifts in pollinator occurrence and their pollen transport effectiveness drive the evolution of mating systems in flowering plants. Understanding the genomic basis of these changes is essential for predicting the persistence of a species under environmental changes. We investigated the genomic changes in Brassica rapa over nine generations of pollination by hoverflies associated with rapid morphological evolution toward the selfing syndrome. We combined a genotyping-by-sequencing (GBS) approach with a genome-wide association study (GWAS) to identify candidate genes, and assessed their functional role in the observed morphological changes by studying mutations of orthologous genes in the model plant Arabidopsis thaliana. We found 31 candidate genes involved in a wide range of functions from DNA/RNA binding to transport. Our functional assessment of orthologous genes in A. thaliana revealed that two of the identified genes in B. rapa are involved in regulating the size of floral organs. We found a protein kinase superfamily protein involved in petal width, an important trait in plant attractiveness to pollinators. Moreover, we found a histone lysine methyltransferase (HKMT) associated with stamen length. Altogether, our study shows that hoverfly pollination leads to rapid evolution toward the selfing syndrome mediated by polygenic changes.