rs3738401

This paper presents CalPen, a web-based tool for calculating penetrance (disease likelihood given a mutation) in complex genetic disorders. The authors validated CalPen against published penetrance calculations for schizophrenia-associated copy number variants (CNVs) and single nucleotide polymorphisms (SNPs). They analyzed 15 CNVs in 39,059 schizophrenia patients and 55,084 controls (average penetrance 7%, ranging from ~1.4% for 15q11.2 deletions to ~20% for 22q11.21 CNVs) and 145 SNPs in 45,405 patients and 122,761 controls (average penetrance 0.7%, with rs1801028 showing the highest at 1.6%).

This is the first systematic study examining the role of DISC1 gene variants in adult ADHD. The intronic SNP rs1538979 was associated with ADHD in a Norwegian sample (OR 1.33, p=0.03) and replicated in a Spanish sample using the tagging SNP rs11122330 (meta-analysis p=0.008, OR 1.25). Additionally, the non-synonymous variant rs6675281 (Phe607Leu) was associated with positive bipolar spectrum symptoms as measured by the Mood Disorder Questionnaire (OR 1.44, p=0.01) in the Norwegian sample, though this was not replicated.