A rare duplication on chromosome 16p11.2 is identified in patients with psychosis in Alzheimer's disease.
Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis.
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Xiaojing
X
Zheng
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
F Yesim
FY
Demirci
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
M Michael
MM
Barmada
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Gale A
GA
Richardson
Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States of America.
Oscar L
OL
Lopez
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States of America.
Robert A
RA
Sweet
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States of America.
M Ilyas
MI
Kamboh
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Eleanor
E
Feingold
D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics*; D058674:Chromosome Duplication; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000150:complications*