The Study of Health in Pomerania (SHIP) comprises the two independent cohorts SHIP-START (recruited between 1997 and 2001) and SHIP-TREND (recruited between 2008 to 2012), which were established to examine the health and disease status of the general adult population in Northeast Germany given that this region had the lowest life expectancy in Germany in the 1990s. ¹ The initial cohort was renamed SHIP-START to avoid confusion with designation of SHIP, as the whole project comprises different cohorts. Both cohorts serve the purpose of understanding the concepts of health and disease in their greatest possible complexity, rather than focusing on specific disease areas. Consequently, the examination programmes are the most comprehensive that have ever been applied to a general population sample worldwide; the baseline examinations of SHIP-TREND took ≤25 h. The second follow-up of SHIP-START (SHIP-START-2) and baseline SHIP-TREND-0 were the first studies worldwide to utilize whole-body magnetic resonance imaging (MRI) in a general population setting. ²

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.