Machine learning methods applied to genotyping data capture interactions between single nucleotide variants in late onset Alzheimer's disease.

Introduction: Genome-wide association studies (GWAS) in late onset Alzheimer's disease (LOAD) provide lists of individual genetic determinants. However, GWAS do not capture the synergistic effects among multiple genetic variants and lack good specificity. Methods: We applied tree-based machine learning algorithms (MLs) to discriminate LOAD (>700 individuals) and age-matched unaffected subjects in UK Biobank with single nucleotide variants (SNVs) from Alzheimer's disease (AD) studies, obtaining specific genomic profiles with the prioritized SNVs. Results: MLs prioritized a set of SNVs located in genes PVRL2, TOMM40, APOE, and APOC1, also influencing gene expression and splicing. The genomic profiles in this region showed interaction patterns involving rs405509 and rs1160985, also present in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. rs405509 located in APOE promoter interacts with rs429358 among others, seemingly neutralizing their predisposing effect. Discussion: Our approach efficiently discriminates LOAD from controls, capturing genomic profiles defined by interactions among SNVs in a hot-spot region.

Analgesic effect of vibration and cooling on pain induced by intraneural electrical stimulation.

Psychophysical experiments were carried out on 16 human subjects to determine how low intensity mechanical and thermal skin stimuli interfere with the sensation of pain. Moderate or intense pain was induced by low frequency (2 Hz) electrical stimulation within cutaneous fascicles of the median nerve at wrist level, and vibration, pressure, cooling or warming were applied for short periods (usually 20-60 sec) within or outside the skin area to which the pain was projected. Vibration within the area of projected pain reduced the sensation of pain more efficiently than vibration outside that area. Moderate pain was sometimes completely inhibited but intense pain was only moderately reduced. Pressure and cooling produced some pain relief whereas mild warming had an ambiguous effect. Since the painful input derived from stimulation of fibres in the nerve trunk, and not from peripheral nociceptors, the pain suppressing effects of vibration and cooling are not explicable in terms of lowered excitability of the nociceptive nerve endings in the skin. Instead, the results indicate that activity in low threshold mechanoreceptive and cold sensitive units suppresses pain at central (probably segmental) levels.