Browsing by Subject "Genetic association study"

Now showing 1 - 4 of 4
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    Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers
    (Springer, 2014) Shen, Li; Thompson, Paul M.; Potkin, Steven G.; Bertram, Lars; Farrer, Lindsay A.; Foroud, Tatiana M.; Green, Robert C.; Hu, Xiaolan; Huentelman, Matthew J.; Kim, Sungeun; Kauwe, John S. K.; Li, Qingqin; Liu, Enchi; Macciardi, Fabio; Moore, Jason H.; Munsie, Leanne; Nho, Kwangsik; Ramanan, Vijay K.; Risacher, Shannon L.; Stone, David J.; Swaminathan, Shanker; Toga, Arthur W.; Weiner, Michael W.; Saykin, Andrew J.; Alzheimer’s Disease Neuroimaging Initiative; Medical and Molecular Genetics, School of Medicine
    The Genetics Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), formally established in 2009, aims to provide resources and facilitate research related to genetic predictors of multidimensional Alzheimer's disease (AD)-related phenotypes. Here, we provide a systematic review of genetic studies published between 2009 and 2012 where either ADNI APOE genotype or genome-wide association study (GWAS) data were used. We review and synthesize ADNI genetic associations with disease status or quantitative disease endophenotypes including structural and functional neuroimaging, fluid biomarker assays, and cognitive performance. We also discuss the diverse analytical strategies used in these studies, including univariate and multivariate analysis, meta-analysis, pathway analysis, and interaction and network analysis. Finally, we perform pathway and network enrichment analyses of these ADNI genetic associations to highlight key mechanisms that may drive disease onset and trajectory. Major ADNI findings included all the top 10 AD genes and several of these (e.g., APOE, BIN1, CLU, CR1, and PICALM) were corroborated by ADNI imaging, fluid and cognitive phenotypes. ADNI imaging genetics studies discovered novel findings (e.g., FRMD6) that were later replicated on different data sets. Several other genes (e.g., APOC1, FTO, GRIN2B, MAGI2, and TOMM40) were associated with multiple ADNI phenotypes, warranting further investigation on other data sets. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future studies employing next-generation sequencing and convergent multi-omics approaches, and for clinical drug and biomarker development.
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    Identifying polymorphic cis-regulatory variants as risk markers for lung carcinogenesis and chemotherapy responses in tobacco smokers from eastern India
    (Springer Nature, 2023-03-10) Sengupta, Debmalya; Mukhopadhyay, Pramiti; Banerjee, Souradeep; Ganguly, Kausik; Mascharak, Prateek; Mukherjee, Noyonika; Mitra, Sangeeta; Bhattacharjee, Samsiddhi; Mitra, Ritabrata; Sarkar, Abhijit; Chaudhuri, Tamohan; Bhattacharjee, Gautam; Nath, Somsubhra; Roychoudhury, Susanta; Sengupta, Mainak; Biochemistry and Molecular Biology, School of Medicine
    Aberrant expression of xenobiotic metabolism and DNA repair genes is critical to lung cancer pathogenesis. This study aims to identify the cis-regulatory variants of the genes modulating lung cancer risk among tobacco smokers and altering their chemotherapy responses. From a list of 2984 SNVs, prioritization and functional annotation revealed 22 cis-eQTLs of 14 genes within the gene expression-correlated DNase I hypersensitive sites using lung tissue-specific ENCODE, GTEx, Roadmap Epigenomics, and TCGA datasets. The 22 cis-regulatory variants predictably alter the binding of 44 transcription factors (TFs) expressed in lung tissue. Interestingly, 6 reported lung cancer-associated variants were found in linkage disequilibrium (LD) with 5 prioritized cis-eQTLs from our study. A case–control study with 3 promoter cis-eQTLs (p < 0.01) on 101 lung cancer patients and 401 healthy controls from eastern India with confirmed smoking history revealed an association of rs3764821 (ALDH3B1) (OR = 2.53, 95% CI = 1.57–4.07, p = 0.00014) and rs3748523 (RAD52) (OR = 1.69, 95% CI = 1.17–2.47, p = 0.006) with lung cancer risk. The effect of different chemotherapy regimens on the overall survival of lung cancer patients to the associated variants showed that the risk alleles of both variants significantly decreased (p < 0.05) patient survival.
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    Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond
    (Springer Nature, 2022-10-07) Gaddis, Nathan; Mathur, Ravi; Marks, Jesse; Zhou, Linran; Quach, Bryan; Waldrop, Alex; Levran, Orna; Agrawal, Arpana; Randesi, Matthew; Adelson, Miriam; Jeffries, Paul W.; Martin, Nicholas G.; Degenhardt, Louisa; Montgomery, Grant W.; Wetherill, Leah; Lai, Dongbing; Bucholz, Kathleen; Foroud, Tatiana; Porjesz, Bernice; Runarsdottir, Valgerdur; Tyrfingsson, Thorarinn; Einarsson, Gudmundur; Gudbjartsson, Daniel F.; Webb, Bradley Todd; Crist, Richard C.; Kranzler, Henry R.; Sherva, Richard; Zhou, Hang; Hulse, Gary; Wildenauer, Dieter; Kelty, Erin; Attia, John; Holliday, Elizabeth G.; McEvoy, Mark; Scott, Rodney J.; Schwab, Sibylle G.; Maher, Brion S.; Gruza, Richard; Kreek, Mary Jeanne; Nelson, Elliot C.; Thorgeirsson, Thorgeir; Stefansson, Kari; Berrettini, Wade H.; Gelernter, Joel; Edenberg, Howard J.; Bierut, Laura; Hancock, Dana B.; Johnson, Eric Otto; Medical and Molecular Genetics, School of Medicine
    Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10-9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
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    Wood cookstove use is associated with gastric cancer in Central America and mediated by host genetics
    (Springer Nature, 2023-10) Rifkin, Samara B.; Miller, Anna K.; Montalvan‑Sanchez, Eleazar E.; Norwood, Dalton A.; Martinez, Enrique; Waterboer, Tim; Beasley, T. Mark; Dominguez, Ricardo L.; Williams, Scott M.; Morgan, Douglas R.; Medicine, School of Medicine
    Biomass cookstove food preparation is linked to aero-digestive cancers, mediated by ingested and inhaled carcinogens (e.g., heterocyclic amines, and polycyclic aromatic hydrocarbons). We investigated the association between gastric adenocarcinoma, wood cookstove use, H. pylori CagA infection and risk modification by variants in genes that metabolize and affect the internal dose of carcinogens. We conducted a population-based, case–control study (814 incident cases, 1049 controls) in rural Honduras, a high-incidence region with a homogeneous diet and endemic H. pylori infection, primarily with the high-risk CagA genotype. We investigated factors including wood cookstove use, H. pylori CagA serostatus, and 15 variants from 7 metabolizing genes, and the interactions between wood stove use and the genetic variants. Male sex (OR 2.0, 1.6–2.6), age (OR 1.04, 1.03–1.05), wood cookstove use (OR 2.3, 1.6–3.3), and CagA serostatus (OR 3.5, 2.4–5.1) and two SNPs in CYP1B1 (rs1800440 and rs1056836) were independently associated with gastric cancer in multivariate analysis. In the final multivariate model, a highly significant interaction (OR 3.1, 1.2–7.8) was noted between wood cookstove use and the rs1800440 metabolizing genotype, highlighting an important gene-environment interaction. Lifetime wood cookstove use associates with gastric cancer risk in the high-incidence regions of Central America, and the association is dependent on the rs1800440 genotype in CYP1B1. H. pylori CagA infection, wood cookstove use and the rs1800440 genotype, all of which are highly prevalent, informs who is at greatest risk from biomass cookstove use.