Browsing by Author "Ma, Yinjiao"

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    Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
    (Nature Publishing Group, 2018-01) Culverhouse, Robert C.; Saccone, Nancy L.; Horton, Amy C.; Ma, Yinjiao; Anstey, Kaarin J.; Banaschewski, Tobias; Burmeister, Margit; Cohen-Woods, Sarah; Etain, Bruno; Fisher, Helen L.; Goldman, Noreen; Guillaume, Sébastien; Horwood, John; Juhasz, Gabriella; Lester, Kathryn J.; Mandelli, Laura; Middeldorp, Christel M.; Olié, Emilie; Villafuerte, Sandra; Air, Tracy M.; Araya, Ricardo; Bowes, Lucy; Burns, Richard; Byrne, Enda M.; Coffey, Carolyn; Coventry, William L.; Gawronski, Katerina; Glei, Dana; Hatzimanolis, Alex; Hottenga, Jouke-Jan; Jaussent, Isabelle; Jawahar, Catharine; Jennen-Steinmetz, Christine; Kramer, John R.; Lajnef, Mohamed; Little, Keriann; zu Schwabedissen, Henriette Meyer; Nauck, Matthias; Nederhof, Esther; Petschner, Peter; Peyrot, Wouter J.; Schwahn, Christian; Sinnamon, Grant; Stacey, David; Tian, Yan; Toben, Catherine; Auwera, Sandra Van der; Wainwright, Nick; Wang, Jen-Chyong; Willemsen, Gonneke; Anderson, Ian M.; Arolt, Volker; Åslund, Cecilia; Bagdy, Gyorgy; Baune, Bernhard T.; Bellivier, Frank; Boomsma, Dorret I.; Courtet, Philippe; Dannlowski, Udo; de Geus, Eco J.C.; Deakin, John F. W.; Easteal, Simon; Eley, Thalia; Fergusson, David M.; Goate, Alison M.; Gonda, Xenia; Grabe, Hans J.; Holzman, Claudia; Johnson, Eric O.; Kennedy, Martin; Laucht, Manfred; Martin, Nicholas G.; Munafò, Marcus; Nilsson, Kent W.; Oldehinkel, Albertine J.; Olsson, Craig; Ormel, Johan; Otte, Christian; Patton, George C.; Penninx, Brenda W.J.H.; Ritchie, Karen; Sarchiapone, Marco; Scheid, JM; Serretti, Alessandro; Smit, Johannes H.; Stefanis, Nicholas C.; Surtees, Paul G.; Völzke, Henry; Weinstein, Maxine; Whooley, Mary; Nurnberger, John I., Jr.; Breslau, Naomi; Bierut, Laura J.; Psychiatry, School of Medicine
    The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 datasets containing 38 802 European-ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analyzed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis1) with qualifying unpublished data were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction, and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalizable, but must be of modest effect size and only observable in limited situations.
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    Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease
    (Oxford University Press, 2023-10-18) Llibre-Guerra, Jorge J.; Iaccarino, Leonardo; Coble, Dean; Edwards, Lauren; Li, Yan; McDade, Eric; Strom, Amelia; Gordon, Brian; Mundada, Nidhi; Schindler, Suzanne E.; Tsoy, Elena; Ma, Yinjiao; Lu, Ruijin; Fagan, Anne M.; Benzinger, Tammie L. S.; Soleimani-Meigooni, David; Aschenbrenner, Andrew J.; Miller, Zachary; Wang, Guoqiao; Kramer, Joel H.; Hassenstab, Jason; Rosen, Howard J.; Morris, John C.; Miller, Bruce L.; Xiong, Chengjie; Perrin, Richard J.; Allegri, Ricardo; Chrem, Patricio; Surace, Ezequiel; Berman, Sarah B.; Chhatwal, Jasmeer; Masters, Colin L.; Farlow, Martin R.; Jucker, Mathias; Levin, Johannes; Fox, Nick C.; Day, Gregory; Gorno-Tempini, Maria Luisa; Boxer, Adam L.; La Joie, Renaud; Rabinovici, Gil D.; Bateman, Randall; Neurology, School of Medicine
    Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases. Our analysis included 117 participants with dominantly inherited Alzheimer's disease enrolled in the Dominantly Inherited Alzheimer Network and 118 individuals with sporadic early-onset Alzheimer's disease enrolled at the University of California San Francisco Alzheimer's Disease Research Center. Baseline differences in clinical and biomarker profiles between both groups were compared using t-tests. Differences in the rates of decline were compared using linear mixed-effects models. Individuals with dominantly inherited Alzheimer's disease exhibited an earlier age-at-symptom onset compared with the sporadic group [43.4 (SD ± 8.5) years versus 54.8 (SD ± 5.0) years, respectively, P < 0.001]. Sporadic cases showed a higher frequency of atypical clinical presentations relative to dominantly inherited (56.8% versus 8.5%, respectively) and a higher frequency of APOE-ε4 (50.0% versus 28.2%, P = 0.001). Compared with sporadic early onset, motor manifestations were higher in the dominantly inherited cohort [32.5% versus 16.9% at baseline (P = 0.006) and 46.1% versus 25.4% at last visit (P = 0.001)]. At baseline, the sporadic early-onset group performed worse on category fluency (P < 0.001), Trail Making Test Part B (P < 0.001) and digit span (P < 0.001). Longitudinally, both groups demonstrated similar rates of cognitive and functional decline in the early stages. After 10 years from symptom onset, dominantly inherited participants experienced a greater decline as measured by Clinical Dementia Rating Sum of Boxes [3.63 versus 1.82 points (P = 0.035)]. CSF amyloid beta-42 levels were comparable [244 (SD ± 39.3) pg/ml dominantly inherited versus 296 (SD ± 24.8) pg/ml sporadic early onset, P = 0.06]. CSF phosphorylated tau at threonine 181 levels were higher in the dominantly inherited Alzheimer's disease cohort (87.3 versus 59.7 pg/ml, P = 0.005), but no significant differences were found for t-tau levels (P = 0.35). In summary, sporadic and inherited Alzheimer's disease differed in baseline profiles; sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline. Despite these differences, shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations, offering valuable insights for future research and clinical trial design.
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    Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage
    (Wiley, 2024) Joseph-Mathurin, Nelly; Feldman, Rebecca L.; Lu, Ruijin; Shirzadi, Zahra; Toomer, Carmen; Saint Clair, Junie R.; Ma, Yinjiao; McKay, Nicole S.; Strain, Jeremy F.; Kilgore, Collin; Friedrichsen, Karl A.; Chen, Charles D.; Gordon, Brian A.; Chen, Gengsheng; Hornbeck, Russ C.; Massoumzadeh, Parinaz; McCullough, Austin A.; Wang, Qing; Li, Yan; Wang, Guoqiao; Keefe, Sarah J.; Schultz, Stephanie A.; Cruchaga, Carlos; Preboske, Gregory M.; Jack, Clifford R., Jr.; Llibre-Guerra, Jorge J.; Allegri, Ricardo F.; Ances, Beau M.; Berman, Sarah B.; Brooks, William S.; Cash, David M.; Day, Gregory S.; Fox, Nick C.; Fulham, Michael; Ghetti, Bernardino; Johnson, Keith A.; Jucker, Mathias; Klunk, William E.; la Fougère, Christian; Levin, Johannes; Niimi, Yoshiki; Oh, Hwamee; Perrin, Richard J.; Reischl, Gerald; Ringman, John M.; Saykin, Andrew J.; Schofield, Peter R.; Su, Yi; Supnet-Bell, Charlene; Vöglein, Jonathan; Yakushev, Igor; Brickman, Adam M.; Morris, John C.; McDade, Eric; Xiong, Chengjie; Bateman, Randall J.; Chhatwal, Jasmeer P.; Benzinger, Tammie L. S.; Dominantly Inherited Alzheimer Network; Pathology and Laboratory Medicine, School of Medicine
    Introduction: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages. Methods: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition. Results: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures. Discussion: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. Highlights: Mutation position influences Aβ burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aβ burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.