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Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Doryanthes palmeri is a giant, flowering succulent herb endemic to north-east NSW and south-east Queensland. Prior to this study, only two D. palmeri sites had been reported in NSW. This study revealed a further nine sites, all of which are restricted to the Mt Warning caldera.
Doryanthes palmeri occurs on infertile lithosols or grows as a lithophyte on bare rock. It occurs in a narrow band of vegetation along the cliff-tops and on steep cliff-faces or rocky ledges in montane heath next to subtropical rainforest, wet sclerophyll forest or warm temperate forest. There are around 6000 mature D. palmeri plants in north-east NSW. Populations at each site occur as clusters on a relatively small amount of the available habitat. The area of occupancy of D. palmeri is less than 1 km2 with an average distance between sites of 6.3 km. However, the distribution consists of four groups of populations with an average of 15 km between the groups suggesting a poor ability to disperse.
There appear to be limits to the extent that plants can expand at some sites which are due mainly to low recruitment of juveniles into the population, illegal seed harvesting and the competition of faster growing native or weed species. The present populations, therefore, are restricted to their current exposed positions. The small restricted, fragmented distribution and current threats to the population suggests that D. palmeri should be regarded as a vulnerable species.