Sex-specific genetic architecture of late-life memory performance.
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Eissman Jaclyn M, Archer Derek B, Mukherjee Shubhabrata, Lee Michael L, Choi Seo-Eun, Scollard Phoebe, Trittschuh Emily H, Mez Jesse B, Bush William S, Kunkle Brian W, Naj Adam C, Gifford Katherine A, Alzheimer's Disease Neuroimaging Initiative (ADNI) | Alzheimer's Disease Genetics Consortium (ADGC) | The Alzheimer's Disease Sequencing Project (ADSP), Cuccaro Michael L, Cruchaga Carlos, Pericak-Vance Margaret A, Farrer Lindsay A, Wang Li-San, Schellenberg Gerard D, Mayeux Richard P, Haines Jonathan L, Jefferson Angela L, Kukull Walter A, Keene C Dirk, Saykin Andrew J, Thompson Paul M, Martin Eden R, Bennett David A, Barnes Lisa L, Schneider Julie A, Crane Paul K, Hohman Timothy J, Dumitrescu Logan
Аннотация
METHODS: We conducted the largest sex-aware genetic study on late-life memory to date (Nmales = 11,942; Nfemales = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants.
RESULTS: We identified three sex-specific loci (rs67099044-CBLN2, rs719070-SCHIP1/IQCJ-SCHIP), including an X-chromosome locus (rs5935633-EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex-specific pathway and found sex-specific genetic correlations between memory and cardiovascular, immune, and education traits.
DISCUSSION: This study showed memory is highly and comparably heritable across sexes, as well as highlighted novel sex-specific genes, pathways, and genetic correlations that related to late-life memory.
HIGHLIGHTS: Demonstrated the heritable component of late-life memory is similar across sexes. Identified two genetic loci with a sex-interaction with baseline memory. Identified an X-chromosome locus associated with memory decline in females. Highlighted sex-specific candidate genes and pathways associated with memory. Revealed sex-specific shared genetic architecture between memory and complex traits.