rs1038026 - TOMM40

Magnitude 4.5 · 8 studies on file

Reported associations

• Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses. - Alzheimer's & dementia : the journal of the Alzheimer's Association (2025) · Willett JDS, Waqas M, Choi Y, Ngai T, Mullin K, Tanzi RE, Prokopenko D · PubMed 39998322

  Alzheimer's disease (AD) is the most prevalent form of dementia. While many AD-associated genetic determinants have been identified, few studies have analyzed individuals of non-European ancestry. We conducted a multi-ancestry genome-wide association study (GWAS) of clinically diagnosed AD and AD-by-proxy using whole genome sequencing data from the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS), National Institute of Mental Health, UK Biobank (UKB), and All of Us (AoU) consisting of 49,149 cases (12,074 clinically diagnosed and 37,075 AD-by-proxy) and 383,225 controls. Nearly half of NIAGADS and AoU participants were of non-European ancestry. For clinically diagnosed AD, we identified 14 new loci-five common (FBN2/SCL27A6, AC090115.1, DYM, KCNG1/AL1

• Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease. - Alzheimer's & dementia : the journal of the Alzheimer's Association (2024) · Archer DB, Eissman JM, Mukherjee S, Lee ML, Choi SE, Scollard P, Trittschuh EH, Mez JB, Bush WS, Kunkle BW, Naj AC, Gifford KA, Cuccaro ML, Pericak-Vance MA, Farrer LA, Wang LS, Schellenberg GD, Mayeux RP, Haines JL, Jefferson AL, Kukull WA, Keene CD, Saykin AJ, Thompson PM, Martin ER, Bennett DA, Barnes LL, Schneider JA, Crane PK, Dumitrescu L, Hohman TJ · PubMed 37985223

  Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance and memory decline. We conducted a cross-ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts. We found high heritability for two ancestry backgrounds. Further, we found a novel ancestry locus for memory decline on chromosome 4 (rs6848524) and three loci in the non-Hispanic Black ancestry group for memory performance on chromosomes 2 (rs111471504), 7 (rs4142249), and 15 (rs74381744). In our gene-level analysis, we found novel genes for memory decline on chromosomes 1 (SLC25A44), 11 (BSX), and 15 (DPP8

• Sex-specific genetic architecture of late-life memory performance. - Alzheimer's & dementia : the journal of the Alzheimer's Association (2024) · Eissman JM, Archer DB, Mukherjee S, Lee ML, Choi SE, Scollard P, Trittschuh EH, Mez JB, Bush WS, Kunkle BW, Naj AC, Gifford KA, Cuccaro ML, Cruchaga C, Pericak-Vance MA, Farrer LA, Wang LS, Schellenberg GD, Mayeux RP, Haines JL, Jefferson AL, Kukull WA, Keene CD, Saykin AJ, Thompson PM, Martin ER, Bennett DA, Barnes LL, Schneider JA, Crane PK, Hohman TJ, Dumitrescu L · PubMed 37984853

  Women demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer's disease. However, the genetic underpinnings of this sex difference in memory performance remain unclear. We conducted the largest sex-aware genetic study on late-life memory to date (N = 11,942; N = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants. We identified three sex-specific loci (rs67099044-CBLN2, rs719070-SCHIP1/IQCJ-SCHIP), including an X-chromosome locus (rs5935633-EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex-

• Better safe than sorry-Whole-genome sequencing indicates that missense variants are significant in susceptibility to COVID-19. - PloS one (2023) · Słomian D, Szyda J, Dobosz P, Stojak J, Michalska-Foryszewska A, Sypniewski M, Liu J, Kotlarz K, Suchocki T, Mroczek M, Stępień M, Sztromwasser P, Król ZJ · PubMed 36662838

  Undoubtedly, genetic factors play an important role in susceptibility and resistance to COVID-19. In this study, we conducted the GWAS analysis. Out of 15,489,173 SNPs, we identified 18,191 significant SNPs for severe and 11,799 SNPs for resistant phenotype, showing that a great number of loci were significant in different COVID-19 representations. The majority of variants were synonymous (60.56% for severe, 58.46% for resistant phenotype) or located in introns (55.77% for severe, 59.83% for resistant phenotype). We identified the most significant SNPs for a severe outcome (in AJAP1 intron) and for COVID resistance (in FIG4 intron). We found no missense variants with a potential causal function on resistance to COVID-19; however, two missense variants were determined as significant a sever

• Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids. - Biological psychiatry (2023) · Davyson E, Shen X, Gadd DA, Bernabeu E, Hillary RF, McCartney DL, Adams M, Marioni R, McIntosh AM · PubMed 36764567

  Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear. We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD. A total of 191 metabolites tested were significantly associated with MDD (false discovery rate-corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There w

• Genetic analyses of diverse populations improves discovery for complex traits. - Nature (2020) · Wojcik GL, Graff M, Nishimura KK, Tao R, Haessler J, Gignoux CR, Highland HM, Patel YM, Sorokin EP, Avery CL, Belbin GM, Bien SA, Cheng I, Cullina S, Hodonsky CJ, Hu Y, Huckins LM, Jeff J, Justice AE, Kocarnik JM, Lim U, Lin BM, Lu Y, Nelson SC, Park SL, Poisner H, Preuss MH, Richard MA, Schurmann C, Setiawan VW, Sockell A, Vahi K, Verbanck M, Vishnu A, Walker RW, Young KL, Zubair N, Acuña-Alonso V, Ambite JL, Barnes KC, Boerwinkle E, Bottinger EP, Bustamante CD, Caberto C, Canizales-Quinteros S, Conomos MP, Deelman E, Do R, Doheny K, Fernández-Rhodes L, Fornage M, Hailu B, Heiss G, Henn BM, Hindorff LA, Jackson RD, Laurie CA, Laurie CC, Li Y, Lin DY, Moreno-Estrada A, Nadkarni G, Norman PJ, Pooler LC, Reiner AP, Romm J, Sabatti C, Sandoval K, Sheng X, Stahl EA, Stram DO, Thornton TA, Wassel CL, Wilkens LR, Winkler CA, Yoneyama S, Buyske S, Haiman CA, Kooperberg C, Le Marchand L, Loos RJF, Matise TC, North KE, Peters U, Kenny EE, Carlson CS · PubMed 31217584

  Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry . In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific . Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to othe

• Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study. - Human molecular genetics (2019) · Kocarnik JM, Richard M, Graff M, Haessler J, Bien S, Carlson C, Carty CL, Reiner AP, Avery CL, Ballantyne CM, LaCroix AZ, Assimes TL, Barbalic M, Pankratz N, Tang W, Tao R, Chen D, Talavera GA, Daviglus ML, Chirinos-Medina DA, Pereira R, Nishimura K, Bužková P, Best LG, Ambite JL, Cheng I, Crawford DC, Hindorff LA, Fornage M, Heiss G, North KE, Haiman CA, Peters U, Le Marchand L, Kooperberg C · PubMed 29878111

  C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ∼200 000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage di

• A large electronic-health-record-based genome-wide study of serum lipids. - Nature genetics (2019) · Hoffmann TJ, Theusch E, Haldar T, Ranatunga DK, Jorgenson E, Medina MW, Kvale MN, Kwok PY, Schaefer C, Krauss RM, Iribarren C, Risch N · PubMed 29507422

  A genome-wide association study (GWAS) of 94,674 ancestrally diverse Kaiser Permanente members using 478,866 longitudinal electronic health record (EHR)-derived measurements for untreated serum lipid levels empowered multiple new findings: 121 new SNP associations (46 primary, 15 conditional, and 60 in meta-analysis with Global Lipids Genetic Consortium data); an increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater impact in females for LDL, HDL, and total cholesterol and the opposite for triglycerides); differences in variance explained among non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistatic interaction, with strong evidence for both at the ABO and FUT2 genes for LDL; and tissue-spe

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