Biology subjects

McGrath, J.

Publications and source records attributed to McGrath, J..

3 recordsLinked to original sources

bioRxiv2017

Higher genetic risk for schizophrenia is associated with living in urban and populated areas

Social stress in urban life has been proposed as an environmental risk factor associated with the increased prevalence of schizophrenia in urban compared to rural areas. However, the potential genetic contributions to this relationship have been largely ignored.\n\nUsing a community-based sample of 15,544 adults living in Australia, we found higher genetic loading for schizophrenia in participants living in more densely populated (p-value=5.69*10-5) or less remote areas (p-value=0.003). Mendelian Randomization suggested that high schizophrenia genetic risk is a causal factor in chosing to live in denser (p-value=0.046) and less remote areas (p-value=0.044).\n\nOur results support the hypothesis of selective migration to more urban environments by people at higher genetic risk for schizophrenia and suggest a need to refine the social stress model for schizophrenia by including genetic influences on where people choose to live.

genetics↗

bioRxiv2017

Causal associations between risk factors and common diseases inferred from GWAS summary data

Health risk factors such as body mass index (BMI), serum cholesterol and blood pressure are associated with many common diseases. It often remains unclear whether the risk factors are cause or consequence of disease, or whether the associations are the result of confounding. Genetic methods are useful to infer causality because genetic variants are present from birth and therefore unlikely to be confounded with environmental factors. We develop and apply a method (GSMR) that performs a multi-SNP Mendelian Randomization analysis using summary-level data from large genome-wide association studies (sample sizes of up to 405,072) to test the causal associations of BMI, waist-to-hip ratio, serum cholesterols, blood pressures, height and years of schooling (EduYears) with a range of common diseases. We identify a number of causal associations including a protective effect of LDL-cholesterol against type-2 diabetes (T2D) that might explain the side effects of statins on T2D, a protective effect of EduYears against Alzheimers disease, and bidirectional associations with opposite effects (e.g. higher BMI increases the risk of T2D but the effect T2D of BMI is negative). HDL-cholesterol has a significant risk effect on age-related macular degeneration, and the effect size remains significant accounting for the other risk factors. Our study develops powerful tools to integrate summary data from large studies to infer causality, and provides important candidates to be prioritized for further studies in medical research and for drug discovery.

genetics↗

bioRxiv2017

The iPSYCH2012 case-cohort sample: New directions for unravelling genetic and environmental architectures of severe mental disorders

The iPSYCH consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born 1981-2005 including 1,472,762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3,540), autism (N=16,146), ADHD (N=18,726), and affective disorder (N=26,380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30,000). Within the sample of 86,189 individuals, a total of 57,377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.

genetics↗