Expressive

rs1048932 - CADM1

Magnitude 2.0 · 8 studies on file

Reported associations

  • Genetic architecture reconciles linkage and association studies of complex traits. - Nature genetics (2024) · Sidorenko J, Couvy-Duchesne B, Kemper KE, Moen GH, Bhatta L, Åsvold BO, Mägi R, Ani A, Wang R, Nolte IM, Gordon S, Hayward C, Campbell A, Benjamin DJ, Cesarini D, Evans DM, Goddard ME, Haley CS, Porteous D, Medland SE, Martin NG, Snieder H, Metspalu A, Hveem K, Brumpton B, Visscher PM, Yengo L · PubMed 39375568

    Linkage studies have successfully mapped loci underlying monogenic disorders, but mostly failed when applied to common diseases. Conversely, genome-wide association studies (GWASs) have identified replicable associations between thousands of SNPs and complex traits, yet capture less than half of the total heritability. In the present study we reconcile these two approaches by showing that linkage signals of height and body mass index (BMI) from 119,000 sibling pairs colocalize with GWAS-identified loci. Concordant with polygenicity, we observed the following: a genome-wide inflation of linkage test statistics; that GWAS results predict linkage signals; and that adjusting phenotypes for polygenic scores reduces linkage signals. Finally, we developed a method using recombination rate-stratif

  • A longitudinal genome-wide association study of bone mineral density mean and variability in the UK Biobank. - Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA (2023) · He D, Liu H, Wei W, Zhao Y, Cai Q, Shi S, Chu X, Qin X, Zhang N, Xu P, Zhang F · PubMed 37500982

    Bone mineral density (BMD) is an essential predictor of osteoporosis and fracture. We conducted a genome-wide trajectory analysis of BMD and analyzed the BMD change. This study aimed to identify the genetic architecture and potential biomarkers of BMD. Our analysis included 141,261 white participants from the UK Biobank with heel BMD phenotype data. We used a genome-wide trajectory analysis tool, TrajGWAS, to conduct a genome-wide association study (GWAS) of BMD. Then, we validated our findings in previously reported BMD genetic associations and performed replication analysis in the Asian participants. Finally, gene-set enrichment analysis (GSEA) of the identified candidate genes was conducted using the FUMA platform. A total of 52 genes associated with BMD trajectory mean were identified,

  • A cross-population atlas of genetic associations for 220 human phenotypes. - Nature genetics (2021) · Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, Narita A, Konuma T, Yamamoto K, Akiyama M, Ishigaki K, Suzuki A, Suzuki K, Obara W, Yamaji K, Takahashi K, Asai S, Takahashi Y, Suzuki T, Shinozaki N, Yamaguchi H, Minami S, Murayama S, Yoshimori K, Nagayama S, Obata D, Higashiyama M, Masumoto A, Koretsune Y, Ito K, Terao C, Yamauchi T, Komuro I, Kadowaki T, Tamiya G, Yamamoto M, Nakamura Y, Kubo M, Murakami Y, Yamamoto K, Kamatani Y, Palotie A, Rivas MA, Daly MJ, Matsuda K, Okada Y · PubMed 34594039

    Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (n = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wid

  • Leveraging Polygenic Functional Enrichment to Improve GWAS Power. - American journal of human genetics (2019) · Kichaev G, Bhatia G, Loh PR, Gazal S, Burch K, Freund MK, Schoech A, Pasaniuc B, Price AL · PubMed 30595370

    Functional genomics data has the potential to increase GWAS power by identifying SNPs that have a higher prior probability of association. Here, we introduce a method that leverages polygenic functional enrichment to incorporate coding, conserved, regulatory, and LD-related genomic annotations into association analyses. We show via simulations with real genotypes that the method, functionally informed novel discovery of risk loci (FINDOR), correctly controls the false-positive rate at null loci and attains a 9%-38% increase in the number of independent associations detected at causal loci, depending on trait polygenicity and sample size. We applied FINDOR to 27 independent complex traits and diseases from the interim UK Biobank release (average N = 130K). Averaged across traits, we attaine

  • Genome-wide association study identifies 112 new loci for body mass index in the Japanese population. - Nature genetics (2017) · Akiyama M, Okada Y, Kanai M, Takahashi A, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, Iwasaki M, Yamaji T, Sawada N, Hachiya T, Tanno K, Shimizu A, Hozawa A, Minegishi N, Tsugane S, Yamamoto M, Kubo M, Kamatani Y · PubMed 28892062

    Obesity is a risk factor for a wide variety of health problems. In a genome-wide association study (GWAS) of body mass index (BMI) in Japanese people (n = 173,430), we found 85 loci significantly associated with obesity (P < 5.0 × 10 ), of which 51 were previously unknown. We conducted trans-ancestral meta-analyses by integrating these results with the results from a GWAS of Europeans and identified 61 additional new loci. In total, this study identifies 112 novel loci, doubling the number of previously known BMI-associated loci. By annotating associated variants with cell-type-specific regulatory marks, we found enrichment of variants in CD19 cells. We also found significant genetic correlations between BMI and lymphocyte count (P = 6.46 × 10 , r = 0.18) and between BMI and multiple com

  • Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program - Unknown journal (n.d.) · Unknown authors · PubMed 39024449

    ABSTRACT: INTRODUCTION: Findings from genome-wide association studies (GWASs) have provided foundational knowledge of the genetic basis of disease, facilitating precision approaches for prevention and treatment. Current GWAS results are limited by underrepresentation of individuals from diverse populations, leading to concerns with generalizability regarding our knowledge of the relationships between genes, traits, and disease. The Department of Veterans Affairs (VA) Million Veteran Program (MVP), one of the largest US-based biobanks, addresses this need; 29% of MVP comprises individuals genetically similar to African (AFR), Admixed American (AMR), and East Asian (EAS) reference populations. With over 635,000 participants and more than 44.3M genotyped variants linked with detailed phenotyp

  • Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation - Unknown journal (n.d.) · Unknown authors · PubMed 38965376

    ABSTRACT: Data within biobanks capture broad yet detailed indices of human variation, but biobank-wide insights can be difficult to extract due to complexity and scale. Here, using large-scale factor analysis, we distill hundreds of variables (diagnoses, assessments and survey items) into 35 latent constructs, using data from unrelated individuals with predominantly estimated European genetic ancestry in UK Biobank. These factors recapitulate known disease classifications, disentangle elements of socioeconomic status, highlight the relevance of psychiatric constructs to health and improve measurement of pro-health behaviours. We go on to demonstrate the power of this approach to clarify genetic signal, enhance discovery and identify associations between underlying phenotypic structure and

  • Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood - Unknown journal (n.d.) · Unknown authors · PubMed 37280435

    ABSTRACT: Aims/hypothesis Determining how high BMI at different time points influences the risk of developing type 2 diabetes and affects insulin secretion and insulin sensitivity is critical. Methods By estimating childhood BMI in 441,761 individuals in the UK Biobank, we identified which genetic variants had larger effects on adulthood BMI than on childhood BMI, and vice versa. All genome-wide significant genetic variants were then used to separate the independent genetic effects of high childhood BMI from those of high adulthood BMI on the risk of type 2 diabetes and insulin-related phenotypes using Mendelian randomisation. We performed two-sample MR using external studies of type 2 diabetes, and oral and intravenous measures of insulin secretion and sensitivity. Results We found tha

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