Publications by authors named "Anders Rosengren"

The NRXN1 locus is a hotspot for non-recurrent copy number variants and exon-disrupting NRXN1 deletions have been associated with increased risk of neurodevelopmental disorders in case-control studies. However, corresponding population-based estimates of prevalence and disease-associated risk are currently lacking. Also, most studies have not differentiated between deletions affecting exons of different NRXN1 splice variants nor considered intronic deletions.

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  • The study analyzes 317 ancient genomes from Mesolithic and Neolithic periods across northern and western Eurasia to understand human migration impacts during the Holocene.* -
  • Findings show a significant genetic divide between eastern and western populations, with the west experiencing major gene replacement due to the introduction of farming, while the east maintained its hunter-gatherer ancestry longer.* -
  • The Yamnaya culture, which emerged around 5,000 BP, played a crucial role in spreading ancestry across western Eurasia, leading to significant genetic changes in European populations.*
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Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (C and N content), mobility (Sr/Sr ratio) and vegetation cover (pollen).

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The 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 genomes, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years.

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The limited understanding of the heterogeneity in the treatment response to antidiabetic drugs contributes to metabolic deterioration and cardiovascular complications, stressing the need for more personalized treatment. Although recent attempts have been made to classify diabetes into subgroups, the utility of such stratification in predicting treatment response is unknown. We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD).

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To address the unmet need for scalable solutions for lifestyle treatment, we developed a new digital method to promote behavioral change. Here we report that patients with type-2 diabetes in Sweden (n = 331) exposed to the intervention have significantly improved HbA1c during a median follow-up of 1038 days (4 mmol/mol compared with matched controls; P = 0.009).

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  • Depression is a prevalent psychiatric disorder and major global disability, and a study involving over 1.3 million people identified 243 genetic risk loci, with 64 being newly discovered, many linked to glutamate and GABA receptor genes targeted by antidepressant medications.
  • The research showed depression is highly polygenic, meaning it's influenced by many genetic variants, with about 11,700 variants accounting for 90% of heritability; many of these variants also affect other psychiatric disorders and educational outcomes.
  • The study highlighted genetic and clinical differences within depression subgroups, indicating those with a higher polygenic burden face significantly increased risks for recurrence and other mental health issues, with notable differences based on sex.
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Objectives: Allele counts of sequence variants obtained by whole genome sequencing (WGS) often play a central role in interpreting the results of genetic and genomic research. However, such variant counts are not readily available for individuals in the Danish population. Here, we present a dataset with allele counts for sequence variants (single nucleotide variants (SNVs) and indels) identified from WGS of 8,671 (5,418 females) individuals from the Danish population.

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  • Autism spectrum disorder (ASD) is diagnosed more often in males than females, and studies suggest a "female protective effect" (FPE) could explain this difference.
  • Research using the Danish iPSYCH resource shows that female ASD cases have siblings with higher ASD rates compared to male ASD cases.
  • Genetic analysis reveals that mothers of ASD cases tend to have higher genetic risk for ASD, supporting the idea that females may be more resilient to inherited genetic factors associated with ASD.
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Sample recruitment for research consortia, biobanks, and personal genomics companies span years, necessitating genotyping in batches, using different technologies. As marker content on genotyping arrays varies, integrating such datasets is non-trivial and its impact on haplotype estimation (phasing) and whole genome imputation, necessary steps for complex trait analysis, remains under-evaluated. Using the iPSYCH dataset, comprising 130,438 individuals, genotyped in two stages, on different arrays, we evaluated phasing and imputation performance across multiple phasing methods and data integration protocols.

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  • ADHD and autism spectrum disorder (ASD) share significant genetic similarities, with researchers identifying seven shared genetic loci and five that differentiate the two conditions.
  • The differentiating loci show opposite genetic effects in ADHD and ASD and are linked to traits like educational achievement and brain volume, while shared genetics correlate with other psychiatric traits.
  • Individuals with both ADHD and ASD exhibit unique genetic patterns, suggesting that understanding these genetic influences can help clarify the biological underpinnings of each disorder and how they may impact cognitive and psychological traits differently.
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Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD.

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  • The study explored genetic variations among 12,893 autistic individuals to better understand the link between genetics and the diverse features of autism.
  • Researchers identified six key factors related to core autism traits, finding that while common genetic variants were linked to these traits, de novo variants were not.
  • The analysis revealed that higher autism polygenic scores (PGS) correlate with a lower chance of co-occurring developmental disabilities, particularly showing that autistic females without intellectual disability inherit more genetic traits than males.
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The lack of effective, scalable solutions for lifestyle treatment is a global clinical problem, causing severe morbidity and mortality. We developed a method for lifestyle treatment that promotes self-reflection and iterative behavioral change, provided as a digital tool, and evaluated its effect in 370 patients with type 2 diabetes (ClinicalTrials.gov identifier: NCT04691973).

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Introduction: The lack of effective, scalable solutions for lifestyle treatment is a global clinical problem, causing severe morbidity and mortality. Digital tools could enable broad utility, but long-term metabolic outcomes and the influence on quality of life are unclear.

Methods: We developed a new method for lifestyle treatment that promotes self-reflection and iterative behavioural change, provided as a digital tool, and evaluated its effect on glycaemic control in patients with type 2 diabetes with HbA1c below 52 mmol/mol (n = 297).

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Aims/hypothesis: Galectin-1 modulates inflammation and angiogenesis, and cross-sectional studies indicate that galectin-1 may be a uniting factor between obesity, type 2 diabetes and kidney function. We examined whether circulating galectin-1 can predict incidence of chronic kidney disease (CKD) and type 2 diabetes in a middle-aged population, and if Mendelian randomisation (MR) can provide evidence for causal direction of effects.

Methods: Participants (n = 4022; 58.

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Background: Although the pathogenic nature of copy number variants (CNVs) on chromosome 22q11.2 has been recognised for decades, unbiased estimates of their population prevalence, mortality, disease risks, and diagnostic trajectories are absent. We aimed to provide the true population prevalence of 22q11.

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We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10); of these, 16 map outside known risk-associated loci. We make two important observations.

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Aims/hypothesis: Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies.

Methods: Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case-control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984-2008).

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Background: Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.

Methods: We did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort.

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To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.

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