Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.
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http://dx.doi.org/10.1038/ncomms7916 | DOI Listing |
Alzheimers Dement
December 2024
Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Background: Several viruses have been linked to Alzheimer disease (AD) by independent lines of evidence.
Method: Whole genome and whole exome sequences (WGS/WES) derived from brain (3,404 AD cases, 894 controls) and blood (15,612 AD cases, 24,544 controls) obtained from European ancestry (EU), African American (AA), Mexican (HMX), South Asian Indian (IND), and Caribbean Hispanic (CH) participants of the Alzheimer's Disease Sequencing Project (ADSP) and 276 AD cases 3,584 controls (all EU) from the Framingham Heart Study (FHS) that did not align to the human reference genome were aligned to viral reference genomes. A genome-wide association study (GWAS) for viral DNA load was conducted using PLINK software and regression models with covariates for sex, age, ancestry principal components, and tissue source.
Alzheimers Dement
December 2024
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) leveraging endophenotypes beyond case/control diagnosis, such as brain amyloid β pathology, have shown promise in identifying novel variants and understanding their potential functional impact. In this study, we leverage two brain amyloid β pathology measurement modalities, PET imaging and neuropathology, to address sample size limitations and to discover novel genetic drivers of disease.
Method: We conducted a meta-analysis on an amyloid PET imaging GWAS (N = 7,036, 35% amyloid positive, 53.
Alzheimers Dement
December 2024
Boston University Alzheimer's Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Background: Alzheimer's disease (AD) has both genetic and environmental risk factors. Gene-environment interaction may help explain some missing heritability. There is strong evidence for cigarette smoking as a risk factor for AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Background: With a rapidly aging population, South Korea anticipates a surge in Alzheimer disease (AD). However, the genetic basis of AD in Koreans is not well understood.
Method: We sequenced the genomes of 3,540 Koreans (1,583 AD cases and 1,957 controls) older than age 60 and performed a genome-wide association study (GWAS) of AD using logistic regression models that included covariates for age, sex, five ancestry principal components, and an empirical genetic relationship matrix.
Alzheimers Dement
December 2024
Stanford University, Stanford, CA, USA.
Background: APOE*4 is the strongest genetic risk for late-onset Alzheimer's disease (AD), but other genetic loci may counter its detrimental effect, providing therapeutic avenues. Expanding beyond non-Hispanic White subjects, we sought to additionally leverage genetic data from non-Hispanic and Hispanic subjects of admixed African ancestry to perform trans-ancestry APOE*4-stratified GWAS, anticipating that allele frequency differences across populations would boost power for gene discovery.
Method: Participants were ages 60+, of European (EU; ≥75%) or admixed African (AFR; ≥25%) ancestry, and diagnosed as cases or controls.
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