Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Late Holocene Dust Deposition Fluxes Over the Entire South Atlantic Ocean

Mineral dust accumulated on the ocean floor is an important archive for reconstructing past atmospheric circulation changes and climatological conditions in the source areas. Dust emitted from Southern Hemisphere dust sources is widely deposited over the oceans. However, there are few records of dust deposition over the open ocean, and a large need for extended geographical coverage exists. We present a large data set (134 surface sediment samples) of Late Holocene dust deposition from seafloor surface sediments covering the entire South Atlantic Ocean. Polymodal grain-size distributions of the lithogenic fraction indicate that the sediments are composed of multiple sediment components. By using end-member modeling, we attempt to disentangle the dust signal from non-aeolian sediments. Combined with 230Th-normalized lithogenic fluxes, we quantified the specific deposition fluxes for mineral dust, crrent-sorted sediments and ice-rafted debris (IRD). Although the method could not completely separate the different components in every region, it shows that dust deposition off the most prominent dust source for the South Atlantic Ocean—southern South America—amounts up to approximately 0.7 g cm−2 Kyr−1 and decreases downwind. Bottom-current-sorted sediments and IRD are mostly concentrated around the continental margins. The ratio of the coarse to fine dust end members reveals input from north African dust sources to the South Atlantic. The majority of the observations are in good agreement with new model simulations. This extensive and relevant data set of dust grain size and deposition fluxes to the South Atlantic could be used to calibrate and validate further model simulations

End-member grain-size distributions used for calculation of end-member composition of South Atlantic surface sediments

This dataset describes the characteristics of the lithogenic components of seafloor surface sediments covering the entire South Atlantic Ocean (from the equator to Antarctica). These samples were collected by multiple seagoing expeditions between1988 and 2005. By using end-member modelling on the multi-modal grain-size distributions, we decomposed the lithogenic fraction into a fine- and coarse-grained dust component, current-sorted sediments and IRD. By multiplying these specific components with 230Th-normalized lithogenic fluxes, we obtained specific fluxes for these four fractions. This allows us to study dust deposition over the remote open ocean more specifically

End-member composition of South Atlantic surface sediments

This dataset describes the characteristics of the lithogenic components of seafloor surface sediments covering the entire South Atlantic Ocean (from the equator to Antarctica). These samples were collected by multiple seagoing expeditions between1988 and 2005. By using end-member modelling on the multi-modal grain-size distributions, we decomposed the lithogenic fraction into a fine- and coarse-grained dust component, current-sorted sediments and IRD. By multiplying these specific components with 230Th-normalized lithogenic fluxes, we obtained specific fluxes for these four fractions. This allows us to study dust deposition over the remote open ocean more specifically

Grain-size distributions, End-member modelling and Th-fluxes of South Atlantic surface sediments

This dataset describes the characteristics of the lithogenic components of seafloor surface sediments covering the entire South Atlantic Ocean (from the equator to Antarctica). These samples were collected by multiple seagoing expeditions between1988 and 2005. By using end-member modelling on the multi-modal grain-size distributions, we decomposed the lithogenic fraction into a fine- and coarse-grained dust component, current-sorted sediments and IRD. By multiplying these specific components with 230Th-normalized lithogenic fluxes, we obtained specific fluxes for these four fractions. This allows us to study dust deposition over the remote open ocean more specifically

Grain-size distributions of South Atlantic surface sediments

This dataset describes the characteristics of the lithogenic components of seafloor surface sediments covering the entire South Atlantic Ocean (from the equator to Antarctica). These samples were collected by multiple seagoing expeditions between1988 and 2005. By using end-member modelling on the multi-modal grain-size distributions, we decomposed the lithogenic fraction into a fine- and coarse-grained dust component, current-sorted sediments and IRD. By multiplying these specific components with 230Th-normalized lithogenic fluxes, we obtained specific fluxes for these four fractions. This allows us to study dust deposition over the remote open ocean more specifically

Lithogenic thorium fluxes into South Atlantic surface sediments

This dataset describes the characteristics of the lithogenic components of seafloor surface sediments covering the entire South Atlantic Ocean (from the equator to Antarctica). These samples were collected by multiple seagoing expeditions between1988 and 2005. By using end-member modelling on the multi-modal grain-size distributions, we decomposed the lithogenic fraction into a fine- and coarse-grained dust component, current-sorted sediments and IRD. By multiplying these specific components with 230Th-normalized lithogenic fluxes, we obtained specific fluxes for these four fractions. This allows us to study dust deposition over the remote open ocean more specifically