Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients, with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1 065 families (containing 1 406 patients with OCD), combined with population-based samples (resulting in a total sample of 5 061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at SNP- and gene-levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13×10−7). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of GWAS signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2, and PTPRD. Analyses at the gene-level revealed association of IQCK and C16orf88 (both P<1×10−6, experiment-wide significant), as well as OFCC1 (P=6.29×10−5). The suggestive findings in this study await replication in larger samples.

Autoimmune thyroid disease (AITD) may be characterized by the measurement in serum of antibodies to thyroid peroxidase. A population of Old Order Amish individuals and families was investigated to determine the prevalence of these antibodies and to examine hypotheses about the mode of transmission of thyroid antibodies. Complex segregation analyses were performed on 4 large multigenerational Old Order Amish families composed of 26 nuclear families containing 199 first degree relatives. Several alternative hypotheses of genetic transmission were examined. Hypotheses of no transmission, polygenic inheritance, single locus transmission, and mixed inheritance were compared. The analyses incorporated population prevalences obtained from a random sample of individuals. Results suggest that the pattern of transmission of thyroid antibodies in these families is consistent with a mixed model in which the major gene is transmitted in an autosomal dominant pattern. The mixed model postulates that there is a single gene of major effect as well as a polygenic component that can act separately and/or together to confer susceptibility for this phenotype. The parameter estimates for the major locus are: gene frequency (q), 0.16 +/- 0.01; maximum male penetrance, 0.35; and maximum female penetrance, 0.70. The heritability of the polygenic background is estimated at 0.41.