X‐chromosome-wide association study for Alzheimer’s disease
Copyright policy )X‐chromosome-wide association study for Alzheimer’s disease
Abstract Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10− 8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10− 6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.
- Charité - University Medicine Berlin Germany
- University of Milan Italy
- University of Alabama at Birmingham United States
- Charles University Czech Republic
- University of Turin Italy
Male, MILD COGNITIVE IMPAIRMENT, mental disorder, Medizin, PROGRESSION, genetics [Alzheimer Disease], methods [Genome-Wide Association Study], FAMILY-HISTORY, X Chromosome Inactivation, DEMENTIA INCIDENCE, genetics [Chromosomes, Human, X], genetics [Genetic Predisposition to Disease], 11 Medical and Health Sciences, info:eu-repo/classification/ddc/610, X-chromosome, Psychiatry, Aged, 80 and over, Biología y Biomedicina / Biología, PREVALENCE, 17 Psychology and Cognitive Sciences, Chemistry, genetics [X Chromosome Inactivation], genetics [Polymorphism, Single Nucleotide], Female, Alzheimer’s disease, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, SEX-DIFFERENCES, 610, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Polymorphism, Single Nucleotide, INACTIVATION PATTERNS, Article, EADB, GR@ACE, DEGESCO, EADI, GERAD, DemGene, FinnGen, ADGC, CHARGE, SDG 3 - Good Health and Well-being, Alzheimer Disease, Humans; Alzheimer Disease/genetics; Genome-Wide Association Study/methods; Female; Chromosomes, Human, X/genetics; Male; Genetic Predisposition to Disease/genetics; Polymorphism, Single Nucleotide/genetics; Aged; X Chromosome Inactivation/genetics; Aged, 80 and over; Case-Control Studies, Humans, Genetic Predisposition to Disease, Biology, METAANALYSIS, Aged, Chromosomes, Human, X, Science & Technology, genome-wide association study, Neurosciences, 3202 Clinical sciences, 06 Biological Sciences, 5203 Clinical and health psychology, RISK LOCI, X chromosome; Alzheimer; genetics, 5202 Biological psychology, Case-Control Studies, Human medicine, Neurosciences & Neurology, TAU, genetic predisposition, Genome-Wide Association Study, ddc: ddc:610
Male, MILD COGNITIVE IMPAIRMENT, mental disorder, Medizin, PROGRESSION, genetics [Alzheimer Disease], methods [Genome-Wide Association Study], FAMILY-HISTORY, X Chromosome Inactivation, DEMENTIA INCIDENCE, genetics [Chromosomes, Human, X], genetics [Genetic Predisposition to Disease], 11 Medical and Health Sciences, info:eu-repo/classification/ddc/610, X-chromosome, Psychiatry, Aged, 80 and over, Biología y Biomedicina / Biología, PREVALENCE, 17 Psychology and Cognitive Sciences, Chemistry, genetics [X Chromosome Inactivation], genetics [Polymorphism, Single Nucleotide], Female, Alzheimer’s disease, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, SEX-DIFFERENCES, 610, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Polymorphism, Single Nucleotide, INACTIVATION PATTERNS, Article, EADB, GR@ACE, DEGESCO, EADI, GERAD, DemGene, FinnGen, ADGC, CHARGE, SDG 3 - Good Health and Well-being, Alzheimer Disease, Humans; Alzheimer Disease/genetics; Genome-Wide Association Study/methods; Female; Chromosomes, Human, X/genetics; Male; Genetic Predisposition to Disease/genetics; Polymorphism, Single Nucleotide/genetics; Aged; X Chromosome Inactivation/genetics; Aged, 80 and over; Case-Control Studies, Humans, Genetic Predisposition to Disease, Biology, METAANALYSIS, Aged, Chromosomes, Human, X, Science & Technology, genome-wide association study, Neurosciences, 3202 Clinical sciences, 06 Biological Sciences, 5203 Clinical and health psychology, RISK LOCI, X chromosome; Alzheimer; genetics, 5202 Biological psychology, Case-Control Studies, Human medicine, Neurosciences & Neurology, TAU, genetic predisposition, Genome-Wide Association Study, ddc: ddc:610
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