Global expression profiling of cognitive level and decline in middle-aged monozygotic twins

A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

“…The enrichment analysis by Starnawska et al (2017) reported four nominally significant gene sets related to neurological functioning, among these "neuroactive ligand receptor interaction, " which was also identified in the present study ( Table 2). The TWAS by Nygaard et al (2019) reported 81 significantly enriched Reactome gene sets for intra-pair difference in cognition, of which 15 were also observed in the present study (see Supplementary Table 6 in Supplementary Material 1). Interestingly, the ten gene sets related to the cell cycle identified in the present study were all reported by Nygaard et al (2019).…”

“…Enrichment analysis was conducted, but no significant gene sets were found. Finally, in a recent TWAS of 470 individuals from the survey of Danish middle-aged and old-aged twins also explored in the present study (Nygaard et al, 2019), the POU6F1 gene was identified as associated with cognitive functioning with suggestive significance (multiple testing corrected p-value = 0.09). Gene set enrichment analysis conducted in this study identified gene sets related to ribosomal proteins, protein metabolism, RNA metabolism, the immune system, and infectious disease as significantly associated with cognitive function.…”

“…The EWAS and TWAS published by Starnawska et al (2017) and Nygaard et al (2019), respectively, investigated study populations (N = 486 and N = 470, respectively) including the 452 twins in the present study population. Both studies performed intra-pair analysis and enrichment analyses of either EWAS or TWAS results, respectively, using KEGG gene sets in the former and Reactome gene sets in the latter.…”

“…The genome-wide methylation data was extracted from a dataset of 492 MADT twins (Soerensen et al, 2019), while the genomewide transcriptome data was extracted from a dataset on 496 MADT twins (Nygaard et al, 2019).…”

“…All the 50,599 probes on the array were annotated using the corresponding annotation file supplied by Agilent. For further details see Nygaard et al (2019).…”