Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease.

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aß) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; ß = 0.35, SE = 0.01, P = 6.2 × 10-311, MAF = 0.19), driven by APOE ɛ4, and five additional novel associations (APOE ε2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE ɛ4. APOE ɛ4 and ε2 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the APOE, we also identified three other genome-wide loci: ABCA7 (rs12151021/chr19p.13.3; ß = 0.07, SE = 0.01, P = 9.2 × 10-09, MAF = 0.32), CR1 (rs6656401/chr1q.32.2; ß = 0.1, SE = 0.02, P = 2.4 × 10-10, MAF = 0.18) and FERMT2 locus (rs117834516/chr14q.22.1; ß = 0.16, SE = 0.03, P = 1.1 × 10-09, MAF = 0.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, ß = 0.79, SE = 0.14, P = 1.4 × 10-08, MAF = 0.006, sex-interaction P = 9.8 × 10-07) and chr11p.15.2 (rs192346166, ß = 0.94, SE = 0.17, P = 3.7 × 10-08, MAF = 0.004, sex-interaction P = 1.3 × 10-03). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.

[Observation on short and long-term effects of cervical spondylotic radiculopathy treated with abdominal acupuncture plus Long's bone-setting manipulation].

OBJECTIVE: To compare the short and long-term therapeutic effects on cervical spondylotic radiculopathy (CSR) treated with simple Long's bone-setting manipulation, abdominal acupuncture and abdominal acupuncture plus Long's bone-setting manipulation. METHODS: One hundred and eighty cases of CSR were randomly allocated into abdominal acupuncture plus bone-setting group (combined therapy group), bone-setting group and abdominal acupuncture group, 60 cases in each group. In combined therapy group, the abdominal acupuncture and Long's bone-setting were applied in combination. Abdominal acupuncture was applied to Zhongwan (CV 12), Guanyuan (CV 4), Shiguan (KI 18), Shangqu (KI 17), etc. Long's manipulation, such as bone-setting in head-upward posture and bone-setting in head-lateral posture, was adopted. In bone-setting group and abdominal acupuncture group, Long's bone-setting manipulation and abdominal acupuncture were adopted simply and respectively. The clinical therapeutic effects were compared after 2 courses of treatment (short-term) and 1-month after treatment (long-term) among groups. RESULTS: The short and long-term curative and markedly effective rates in combined therapy group were 80.7% (46/57) and 68.4% (39/57) respectively, which were better than those of 63.64% (35/55), 30.9% (17/55) in bone-setting group and 58.9% (33/56), 50.0% (28/56) in abdominal acupuncture group, separately (all P < 0.05). Moreover, the long-term curative and markedly effective rate in abdominal acupuncture group was superior to that in bone-setting group (P < 0.05). CONCLUSION: Abdominal acupuncture plus Long's bone-setting manipulation has significant efficacy of either short or long-term on CSR, which is superior to the efficacy of either simple abdominal acupuncture or Long's bone-setting manipulation and indicates superimposed effect. Hence, it is one of the better approaches in CSR treatment.