This study is one example of many where Cochran and his lab are attempting to right-size representation of underrepresented populations in genetic association studies. This study is an association study for age at dementia onset in dominant early-onset Alzheimer’s disease. Key findings include the observation that both rare and common genetic variations can associate with the age of onset for dominant Alzheimer’s, despite the strong nature of dominant Alzheimer’s mutations.

Cochran, J.N.*, Acosta-Uribe, J.*, Madrigal, L., Aguillón, D., et al. “Genetic Associations with Age at Dementia Onset in the PSEN1 E280A Colombian Kindred,” Under initial review at Lancet Neurology (also on medRxiv, doi: 10.1101/2020.09.23.20198424).

This collaborative effort with the University of California, Santa Barbara, and the University of Antioquia in Colombia identified 21 pathogenic variants in neurodegeneration-associated genes from a group of 900 patients with neurodegenerative disease from Colombia.

Acosta-Uribe J, Aguillón D, Cochran JN, … Myers RM, Browning SR, Lopera F, Kosik KS. A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects. Genome Med. 2022 Mar 8;14(1):27. doi: 10.1186/s13073-022-01035-9.

This paper uses genome-wide approaches to search for associations of rare non-coding variation with disease risk. It is also an example of how the Cochran lab works collaboratively with other groups on a cohort of individuals with early-onset Alzheimer’s disease or frontotemporal dementia. Please note important caveats of this study pointed out in PMID 32888507 and 32888508.

Cochran JN, Geier EG, Bonham LW, Alzheimer’s Disease Neuroimaging Initiative et al. “Non-coding and Loss-of-Function Coding Variants in TET2 are Associated with Multiple Neurodegenerative Diseases,” Am J Hum Genet. 2020 May 7;106(5):632-645. doi: 10.1016/j.ajhg.2020.03.010. Epub 2020 Apr 23.PMID: 32330418