Microduplications at the 15q11.2 BP1-BP2 locus are enriched in patients with anorexia nervosa

Xiao Chang; Huiqi Qu; Yichuan Liu; Joseph Glessner; Cuiping Hou; Fengxiang Wang; Jin Li; Patrick Sleiman; Hakon Hakonarson

doi:10.1016/j.jpsychires.2019.01.021

Microduplications at the 15q11.2 BP1-BP2 locus are enriched in patients with anorexia nervosa

J Psychiatr Res. 2019 Jun:113:34-38. doi: 10.1016/j.jpsychires.2019.01.021. Epub 2019 Jan 29.

Authors

Xiao Chang¹, Huiqi Qu¹, Yichuan Liu¹, Joseph Glessner¹, Cuiping Hou¹, Fengxiang Wang¹, Jin Li², Patrick Sleiman³, Hakon Hakonarson⁴

Affiliations

¹ The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
² Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
³ The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
⁴ The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. Electronic address: Hakonarson@chop.edu.

Abstract

Microduplication at 15q11.2 have been reported in genetic association studies of schizophrenia and autism. Given the potential overlap in psychiatric symptoms of schizophrenia and autism with anorexia nervosa (AN), we were inspired to test the association of this CNV locus with the genetic susceptibility of AN using ParseCNV, a highly quality controlled CNV pipeline developed by our group. The CNV analysis was performed in 1017 AN cases and 7250 controls using the Illumina HumanHap610 SNP arrays data. We uncovered association of the 15q11.2 microduplication with AN with P = 0.00023, while no genetic association between the microdeletion of this region and AN was identified. Among four genes in this region that are not imprinted, NIPA1 has the highest expression in brain and encodes a magnesium transporter protein on early endosomes and the cell surface in neurons. Targeting at Mg²⁺ uptake mediated by NIPA1 presents an interesting research topic for the explorations of novel therapy for AN and other neurobehavioral diseases, such as schizophrenia and autism.

Keywords: Anorexia nervosa; CYFIP1; Copy number variation; NIPA1; NIPA2.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anorexia Nervosa / genetics*
Chromosome Duplication / genetics*
Chromosomes, Human, Pair 15 / genetics*
DNA Copy Number Variations / genetics
Female
Humans
Male

Grants and funding

U01 HG008684/HG/NHGRI NIH HHS/United States