Genome-wide Association Study Implicates HLA-C*01:02 as a Risk Factor at the Major Histocompatibility Complex Locus in Schizophrenia

BACKGROUND: We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. METHODS: The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. RESULTS: One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10(-9) and in combined samples (rs2523722 p combined = 2.88 × 10(-16)) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. CONCLUSIONS: This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci.

Warts in general practice

Eight hundred and ninety seven patients referred by their general practitioner to Health Centre Wart Clinics were interviewed. Seventy one patients (7.9%) were found to have lesions other than cutaneous warts. Females were significantly more likely to have plantar warts on their toes (p less than 0.002) and non-plantar warts on their fingers (p less than 0.03) and less likely to have non-plantar warts on the palms of their hands (p less than 0.03) than males. Patients living in large households (5+ persons) were more likely than patients living in smaller households (2-4 persons) to report an infected co-habitant (p less than 0.001). Patients with periungual warts were significantly more likely to be nailbiters. (p less than 0.001). Patients presenting with warts greater than two years in duration were more likely to have multiple warts than those with warts less than one month in duration (p less than 0.001). Patients who frequently immersed their hands in water were more likely to present with multiple warts on the hands (p less than 0.001). Multiple plantar warts were associated with moist or macerated feet (p less than 0.001). The role of the family doctor in diagnosing and preventing the spread of this infection is discussed.

Help needed in medication self-management for people with visual impairment: case-control study

Background: Visual impairment (VI) is rising in prevalence and contributing to increasing morbidity, particularly among older people. Understanding patients' problems is fundamental to achieving optimal health outcomes but little is known about how VI impacts on self-management of medication.

Aim: To compare issues relating to medication self-management between older people with and without VI.

Design and setting: Case-control study with participants aged =65 years, prescribed at least two long-term oral medications daily, living within the community.

Method: The study recruited 156 patients with VI (best corrected visual acuity [BCVA] 6/18 to 3/60) at low-vision clinics; community optometrists identified 158 controls (BCVA 6/9 or better). Researchers visited participants in their homes, administered two validated questionnaires to assess medication adherence (Morisky; Medication Adherence Report Scale [MARS]), and asked questions about medication self-management, beliefs, and support.

Results: Approximately half of the participants in both groups reported perfect adherence on both questionnaires (52.5% Morisky; 43.3%, MARS). Despite using optical aids, few (3%) with VI could read medication information clearly; 24% had difficulty distinguishing different tablets. More people with VI (29%) than controls (13%) (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.6 to 5.0) needed help managing their medication, from friends (19% versus 10%) or pharmacists (10% versus 2.5%; OR = 4.4, 95% CI = 1.4 to 13.5); more received social service support (OR = 7.1; 95% CI = 3.9 to 12.9).

Conclusion: Compared to their peers without VI, older people with VI are more than twice as likely to need help in managing medication. In clinical practice in primary care, patients' needs for practical support in taking prescribed treatment must be recognised. Strategies for effective medication self-management should be explored.

The role of ECE1 variants in cognitive ability in old age and Alzheimer's disease risk

The ß-amyloid peptide may play a central role in Alzheimer's disease (AD) pathogenesis. We have evaluated variants in seven Aß-degrading genes (ACE, ECE1, ECE2, IDE, MME, PLAU, and TF) for association with AD risk in the Genetic and Environmental Risk in Alzheimer's Disease Consortium 1 (GERAD1) cohort, and with three cognitive phenotypes in the Lothian Birth Cohort 1936 (LBC1936), using 128 and 121 SNPs, respectively. In GERAD1, we identified a significant association between a four-SNP intragenic ECE1 haplotype and risk of AD in individuals that carried at least one APOE e4 allele (P = 0.00035, odds ratio = 1.61). In LBC1936, we identified a significant association between a different two-SNP ECE1 intragenic haplotype and non-verbal reasoning in individuals lacking the APOE e4 allele (P = 0.00036, ß = -0.19). Both results showed a trend towards significance after permutation (0.05 <P <0.10). A follow-up cognitive genetic study evaluated the association of ECE1 SNPs in three additional cohorts of non-demented older people. Meta-analysis of the four cohorts identified the significant association (Z <0.05) of SNPs in the ECE-1b promoter with non-verbal reasoning scores, particularly in individuals lacking the APOE e4 allele. Our genetic findings are not wholly consistent. Nonetheless, the AD associated intronic haplotype is linked to the 338A variant of known ECE1b promoter variant, 338C>A (rs213045). We observed significantly less expression from the 338A variant in two human neuroblastoma cell lines and speculate that this promoter may be subject to tissue-specific regulation.