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- Hagenbeek, FA, et al.
(författare)
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Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 39-
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
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- Jongs, N, et al.
(författare)
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A framework for assessing neuropsychiatric phenotypes by using smartphone-based location data
- 2020
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 211-
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Tidskriftsartikel (refereegranskat)abstract
- The use of smartphone-based location data to quantify behavior longitudinally and passively is rapidly gaining traction in neuropsychiatric research. However, a standardized and validated preprocessing framework for deriving behavioral phenotypes from smartphone-based location data is currently lacking. Here, we present a preprocessing framework consisting of methods that are validated in the context of geospatial data. This framework aims to generate context-enriched location data by identifying stationary, non-stationary, and recurrent stationary states in movement patterns. Subsequently, this context-enriched data is used to derive a series of behavioral phenotypes that are related to movement. By using smartphone-based location data collected from 245 subjects, including patients with schizophrenia, we show that the proposed framework is effective and accurate in generating context-enriched location data. This data was subsequently used to derive behavioral readouts that were sensitive in detecting behavioral nuances related to schizophrenia and aging, such as the time spent at home and the number of unique places visited. Overall, our results indicate that the proposed framework reliably preprocesses raw smartphone-based location data in such a manner that relevant behavioral phenotypes of interest can be derived.
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- Pellikaan, K, et al.
(författare)
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Hypogonadism in Women with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion
- 2021
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:24
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Tidskriftsartikel (refereegranskat)abstract
- Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.
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- van de Kreeke, JA, et al.
(författare)
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Optical coherence tomography angiography in preclinical Alzheimer's disease
- 2020
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Ingår i: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 104:2, s. 157-161
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Tidskriftsartikel (refereegranskat)abstract
- As a protrusion from the brain, the retina might reflect the status of the brain. Previous studies showed a decrease in vessel density and foveal avascular zone (FAZ) enlargement on optical coherence tomography angiography (OCTA) in individuals suffering from Alzheimer’s disease (AD). This study aims to assess whether such changes are already present in preclinical stages of AD, in a population of monozygotic (MZ) twins.Methods124 cognitively healthy individuals (MZ twins, ages 60–93 years) underwent [18F]flutemetamol amyloid positron emission tomography (PET) scanning and OCTA. PET scans were visually rated for cortical amyloid-beta (Aβ) positivity. Parametric global cortical non-displaceable binding potential (BPND) was used as a continuous measure for Aβ aggregation. FAZ size and vessel densities for the inner and outer ring of the macular ETDRS grid and in a 3–6 mm ring around the optic nerve head (ONH) were measured.OCTA measures were associated with visual Aβ score,BPNDand amyloid load estimated by twin concordance on visual Aβ score. Twin correlations were estimated as a measure of maximum heritability of OCTA measures.Results13 of 124 participants were Aβ+. Aβ+ individuals had significantly higher vessel density than Aβ– individuals in all regions but did not differ in FAZ size. Twin analyses showed a positive association between and vessel densities in all regions.BPNDtended to be associated with higher vessel density in the inner ring. Twin correlations were moderate/high for all OCTA parameters except vessel density around the ONH, which correlated weakly.ConclusionRetinal vessel density was higher in individuals with preclinical AD.
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