Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.

Autor:	Main LR; Departments of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, USA, 44106.; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016.; Cleveland Institute of Computational Biology, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44106., Song YE; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016.; Cleveland Institute of Computational Biology, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44106., Lynn A; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016.; Cleveland Institute of Computational Biology, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44106., Laux RA; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016., Miskimen KL; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016., Osterman MD; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016., Cuccaro ML; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Ogrocki PK; Department of Neurology, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH, USA, 44106.; Department of Neurology, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44106., Lerner AJ; Department of Neurology, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH, USA, 44106.; Department of Neurology, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44106., Vance JM; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Fuzzell MD; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016., Fuzzell SL; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016., Hochstetler SD; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016., Dorfsman DA; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Caywood LJ; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Prough MB; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Adams LD; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Clouse JE; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Herington SD; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Scott WK; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Pericak-Vance MA; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, USA, 33136., Haines JL; Departments of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, USA, 44106.; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44016.; Cleveland Institute of Computational Biology, Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, USA, 44106.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Dec 14. Date of Electronic Publication: 2023 Dec 14.
DOI:	10.1101/2023.12.13.23299932
Abstrakt:	Introduction: Alzheimer disease (AD) remains a debilitating condition with limited treatments and additional therapeutic targets needed. Identifying AD protective genetic loci may identify new targets and accelerate identification of therapeutic treatments. We examined a founder population to identify loci associated with cognitive preservation into advanced age. Methods: Genome-wide association and linkage analyses were performed on 946 examined and sampled Amish individuals, aged 76-95, who were either cognitively unimpaired (CU) or impaired (CI). Results: 12 SNPs demonstrated suggestive association (P≤5×10 -4 ) with cognitive preservation. Genetic linkage analyses identified >100 significant (LOD≥3.3) SNPs, some which overlapped with the association results. Only one locus on chromosome 2 retained significance across multiple analyses. Discussion: A novel significant result for cognitive preservation on chromosome 2 includes the genes LRRTM4 and CTNNA2 . Additionally, the lead SNP, rs1402906, impacts the POU3F2 transcription factor binding affinity, which regulates LRRTM4 and CTNNA2 . Competing Interests: 8CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest.
Databáze:	MEDLINE
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