The power of genetic knowledge of a population: A lesson from the Generation study 2

• Published in: Alzheimer's & Dementia
• Main Authors: Snædal, Jón, Thordardottir, Steinunn, Eyjolfsdottir, Helga, Gislason, Thorstein
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2020
• Subjects: Iceland
• Online Access: http://dx.doi.org/10.1002/alz.043011; https://onlinelibrary.wiley.com/doi/pdf/10.1002/alz.043011

Abstract Background Alzheimer´s Prevention Initiative Generation Program enrolled ApoE4 carriers to focus on individuals with highest likelihood for the disease. The greatest risk for sporadic AD is among ApoE4 carriers, primarily homozygotes (HM) but to some extent for heterozygotes (HT). Frequency of HM is 2‐3% in Caucasians and HT in about 24%, making it difficult to identify suitable participants. DeCode Genetics has collected samples from 160.000 individuals (Iceland pop. 360.000). More than 50.000 have been analysed by whole genome sequencing, allowing targeted invitation to participate in the Generation Study 2. Our site was selected for enrolment of 200 participants (10% of total planned in the study). Method From the genetic database of DeCode, individuals were selected after un‐coding by an independent data committee. Of those 1000 (45%) were HM for ApoE4, 1000 (45%) were HT. 200 (10%) non‐carriers were also selected to maintain study site blinded to the genetic status. Individuals meeting eligibility criteria were contacted by phone. Written information was sent if interested, followed by invitation for the screening visit at the site. Result Over the selected 2.200 individuals, 315 cases (15.0%) met an exclusion criteria based on their medical records. Of 1749 individuals approached by telephone, 883 (51,5%) declined to receive further information. Letters were sent to 866 individuals out of which 516 (60%) consented to participate in the study. Screening started with confirmation of the ApoE4 genotype and disclosure to the participant. Amyloid status was tested by lumbar puncture or PET scan when it became available. In July 2019, treatment with umibecestat in the Generation program was terminated. At that point, ApoE4 status had been disclosed to 432 participants (HM 38%, HT 54%, NC 8%). A total of 129 participants had been randomized of which 98 were HM and 31 HT with elevated amyloid. 150 participants were still in the screening phase. Conclusion Extensive knowledge of the genetic information in ...