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Genetic and regulatory architecture of Alzheimer's disease in the region.
Monday,2020-08-24 18:22 America/Los_Angeles — ecterry
| Title | Genetic and regulatory architecture of Alzheimer's disease in the region. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Kulminski, AM, Shu, L, Loika, Y, He, L, Nazarian, A, Arbeev, K, Ukraintseva, S, Yashin, A, Culminskaya, I |
| Journal | Alzheimers Dement (Amst) |
| Volume | 12 |
| Issue | 1 |
| Pagination | e12008 |
| Date Published | 2020 |
| ISSN | 2352-8729 |
| Abstract | <p><b>Introduction: </b>Apolipoprotein E () ε2 and ε4 alleles encoded by rs7412 and rs429358 polymorphisms, respectively, are landmark contra and pro "risk" factors for Alzheimer's disease (AD).</p><p><b>Methods: </b>We examined differences in linkage disequilibrium (LD) structures between (1) AD-affected and unaffected subjects and (2) older AD-unaffected and younger subjects in the 19q13.3 region harboring rs7412 and rs429358.</p><p><b>Results: </b>AD is associated with sex-nonspecific heterogeneous patterns of decreased and increased LD of rs7412 and rs429358, respectively, with other polymorphisms from five genes in this region in AD-affected subjects. The LD patterns in older AD-unaffected subjects resembled those in younger individuals. Polarization of the ε4- and ε2 allele-related heterogeneous LD clusters differentiated cell types and implicated specific tissues in AD pathogenesis.</p><p><b>Discussion: </b>Protection and predisposition to AD is characterized by an interplay of rs7412 and rs429358, with multiple polymorphisms in the 19q13.3 region in a tissue-specific manner, which is not driven by common evolutionary forces.</p> |
| DOI | 10.1002/dad2.12008 |
| Alternate Journal | Alzheimers Dement (Amst) |
| PubMed ID | 32211503 |
| PubMed Central ID | PMC7085286 |
| Grant List | HHSN268201500001C / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201500001I / HL / NHLBI NIH HHS / United States P01 AG043352 / AG / NIA NIH HHS / United States RC2 AG036495 / AG / NIA NIH HHS / United States R01 AG047310 / AG / NIA NIH HHS / United States R01 AG061853 / AG / NIA NIH HHS / United States RC4 AG039029 / AG / NIA NIH HHS / United States UL1 RR033176 / RR / NCRR NIH HHS / United States U01 AG009740 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States |
ePub date:
20/02