Microduplications at the 15q11.2 BP1-BP2 Locus are Enriched in Patients with Anorexia Nervosa

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 PareseCNV, a highly quality controlled CNV pipeline developed by our group. The CNV analysis was performed in 1,017 AN cases and 7,250 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 asschizophrenia and autism. Funding: The study was supported by Institutional Development Funds from the Children’s Hospital of Philadelphia to the Center for Applied Genomics, The Children’s Hospital of Philadelphia Endowed Chair in Genomic Research to HH and by U01HG006830 from the NHGRI (eMERGE). Declaration of Interest: None declared. Ethical Approval: This study was approved by the Research Ethics Board of the Children's Hospital of Philadelphia.