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Sep 13, 2024 | 
biorxiv.org | Simone Montalbano |Andrés Ingason |Thomas Werge |Jesper Gaadin
AbstractMotivationFor more than a decade, running PennCNV on SNP array data has been the gold standard for detecting Copy Number Variants (CNVs, deletions and duplications). It is generally assumed that PennCNV has high sensitivity but poor specificity, leading to a large portion of CNV calls being false positives. Researchers often rely on manual inspection of the raw data trends to validate CNV calls. However, this approach is not feasible for more than a handful of loci in large collections.
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Jun 16, 2024 | 
nature.com | Jacob Bergstedt |Ziyan Ma |Shuyang Yao |Nadine Staples Parker |Oleksandr Frei |Joeri J. Meijsen | +12 more
AbstractMajor depressive disorder (MDD) and cardiovascular disease (CVD) are often comorbid, resulting in excess morbidity and mortality. Here we show that CVDs share most of their genetic risk factors with MDD. Multivariate genome-wide association analysis of shared genetic liability between MDD and atherosclerotic CVD revealed seven loci and distinct patterns of tissue and brain cell-type enrichments, suggesting the involvement of the thalamus.
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Jun 12, 2024 | 
nature.com | Joeri J. Meijsen |Kejia Hu |Morten Krebs |Georgios Athanasiadis |Sarah Washbrook |Richard Zetterberg | +14 more
AbstractMental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders.
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Feb 26, 2024 | 
nature.com | Clara Albiñana |Zhihong Zhu |Nis Borbye-Lorenzen |Kristin Skogstrand |Naomi R. Wray |Joana A. Revez | +7 more
Correction to: Nature Communications https://doi.org/10.1038/s41467-023-36392-5, published online 15 February 2023The original version of this article contained an error in the second paragraph of the ‘Assay of DBP concentration’ section of the ‘Methods’, which incorrectly read ‘The lower and upper detection limits for DBP were 2.07 and 79.8 mg/L respectively’. The correct version states ‘2.07 µg/L’ in place of ‘2.07’. This has been corrected in both the PDF and HTML versions of the article.
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Jan 10, 2024 | 
nature.com | Evan K. Irving-Pease |Anders Fischer |Karl-Göran Sjögren |Alma Halgren |Ruairidh Macleod |Rasmus Henriksen | +14 more
AbstractThe Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia.
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Nov 29, 2023 | 
nature.com | Clare Palmer |Morten Krebs |Vivek Appadurai |Esben Agerbo |Anders D. Børglum |David M. Hougaard | +7 more
AbstractAttention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals. First, we identify one genome-wide significant locus by comparing cases with ADHD and autism spectrum disorder (ASD) to cases with ADHD but not ASD.
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Nov 20, 2023 | 
nature.com | Andrew Dahl |Ulzee An |Morten Krebs |Vivek Appadurai |Silviu-Alin Bacanu |Thomas Werge | +3 more
AbstractBiobanks often contain several phenotypes relevant to diseases such as major depressive disorder (MDD), with partly distinct genetic architectures. Researchers face complex tradeoffs between shallow (large sample size, low specificity/sensitivity) and deep (small sample size, high specificity/sensitivity) phenotypes, and the optimal choices are often unclear. Here we propose to integrate these phenotypes to combine the benefits of each.
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Nov 12, 2023 | 
nature.com | Clara Albiñana |Bjarni J Vilhjálmsson |Thomas Werge |David M. Hougaard |Anders D. Børglum |Preben mortensen | +1 more
AbstractIt remains inconclusive whether postpartum depression (PPD) and depression with onset outside the postpartum period (MDD) are genetically distinct disorders. We aimed to investigate whether polygenic risk scores (PGSs) for major mental disorders differ between PPD cases and MDD cases in a nested case-control study of 50,057 women born from 1981 to 1997 in the iPSYCH2015 sample in Demark.
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Oct 5, 2023 | 
nature.com | Robin Beaumont |Christopher Flatley |Marc Vaudel |JING CHEN |Gunn-Helen Moen |Line Skotte | +52 more
AbstractA well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1.
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Sep 9, 2023 | 
nature.com | Emil M Pedersen |David M. Hougaard |Thomas Werge |Anders D. Børglum |Katherine L. Musliner |Andrea Ganna | +3 more
AbstractProportional hazards models have been proposed to analyse time-to-event phenotypes in genome-wide association studies (GWAS). However, little is known about the ability of proportional hazards models to identify genetic associations under different generative models and when ascertainment is present. Here we propose the age-dependent liability threshold (ADuLT) model as an alternative to a Cox regression based GWAS, here represented by SPACox.
