التفاصيل البيبلوغرافية
| العنوان: |
Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies LRRC4C, LHX5-AS1 and nominates ancestry-specific loci PTPRK , GRB14 , and KIAA0825 as novel risk loci for Alzheimer's disease: the Alzheimer's Disease Genetics Consortium. |
| المؤلفون: |
Rajabli F, Benchek P, Tosto G, Kushch N, Sha J, Bazemore K, Zhu C, Lee WP, Haut J, Hamilton-Nelson KL, Wheeler NR, Zhao Y, Farrell JJ, Grunin MA, Leung YY, Kuksa PP, Li D, Lucio da Fonseca E, Mez JB, Palmer EL, Pillai J, Sherva RM, Song YE, Zhang X, Iqbal T, Pathak O, Valladares O, Kuzma AB, Abner E, Adams PM, Aguirre A, Albert MS, Albin RL, Allen M, Alvarez L, Apostolova LG, Arnold SE, Asthana S, Atwood CS, Ayres G, Baldwin CT, Barber RC, Barnes LL, Barral S, Beach TG, Becker JT, Beecham GW, Beekly D, Benitez BA, Bennett D, Bertelson J, Bird TD, Blacker D, Boeve BF, Bowen JD, Boxer A, Brewer J, Burke JR, Burns JM, Buxbaum JD, Cairns NJ, Cantwell LB, Cao C, Carlson CS, Carlsson CM, Carney RM, Carrasquillo MM, Chasse S, Chesselet MF, Chin NA, Chui HC, Chung J, Craft S, Crane PK, Cribbs DH, Crocco EA, Cruchaga C, Cuccaro ML, Cullum M, Darby E, Davis B, De Jager PL, DeCarli C, DeToledo J, Dick M, Dickson DW, Dombroski BA, Doody RS, Duara R, Ertekin-Taner N, Evans DA, Faber KM, Fairchild TJ, Fallon KB, Fardo DW, Farlow MR, Fernandez-Hernandez V, Ferris S, Foroud TM, Frosch MP, Fulton-Howard B, Galasko DR, Gamboa A, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Goate AM, Grabowski TJ, Graff-Radford NR, Green RC, Growdon JH, Hakonarson H, Hall J, Hamilton RL, Harari O, Hardy J, Harrell LE, Head E, Henderson VW, Hernandez M, Hohman T, Honig LS, Huebinger RM, Huentelman MJ, Hulette CM, Hyman BT, Hynan LS, Ibanez L, Jarvik GP, Jayadev S, Jin LW, Johnson K, Johnson L, Kamboh MI, Karydas AM, Katz MJ, Kauwe JS, Kaye JA, Keene CD, Khaleeq A, Kim R, Knebl J, Kowall NW, Kramer JH, Kukull WA, LaFerla FM, Lah JJ, Larson EB, Lerner A, Leverenz JB, Levey AI, Lieberman AP, Lipton RB, Logue M, Lopez OL, Lunetta KL, Lyketsos CG, Mains D, Margaret FE, Marson DC, Martin ERR, Martiniuk F, Mash DC, Masliah E, Massman P, Masurkar A, McCormick WC, McCurry SM, McDavid AN, McDonough S, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Montine TJ, Monuki ES, Morris JC, Mukherjee S, Myers AJ, Nguyen T, O'Bryant S, Olichney JM, Ory M, Palmer R, Parisi JE, Paulson HL, Pavlik V, Paydarfar D, Perez V, Peskind E, Petersen RC, Pierce A, Polk M, Poon WW, Potter H, Qu L, Quiceno M, Quinn JF, Raj A, Raskind M, Reiman EM, Reisberg B, Reisch JS, Ringman JM, Roberson ED, Rodriguear M, Rogaeva E, Rosen HJ, Rosenberg RN, Royall DR, Sager MA, Sano M, Saykin AJ, Schneider JA, Schneider LS, Seeley WW, Slifer SH, Small S, Smith AG, Smith JP, Sonnen JA, Spina S, St George-Hyslop P, Stern RA, Stevens AB, Strittmatter SM, Sultzer D, Swerdlow RH, Tanzi RE, Tilson JL, Trojanowski JQ, Troncoso JC, Tsuang DW, Van Deerlin VM, van Eldik LJ, Vance JM, Vardarajan BN, Vassar R, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Whitehead PL, Wijsman EM, Wilhelmsen KC, Williams B, Williamson J, Wilms H, Wingo TS, Wisniewski T, Woltjer RL, Woon M, Wright CB, Wu CK, Younkin SG, Yu CE, Yu L, Zhu X, Kunkle BW, Bush WS, Wang LS, Farrer LA, Haines JL, Mayeux R, Pericak-Vance MA, Schellenberg GD, Jun GR, Reitz C, Naj AC |
| المصدر: |
MedRxiv : the preprint server for health sciences [medRxiv] 2023 Jul 08. Date of Electronic Publication: 2023 Jul 08. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in non-European ancestry groups in genome-wide association studies (GWAS). We constructed and analyzed a multi-ancestry GWAS dataset in the Alzheimer's Disease (AD) Genetics Consortium (ADGC) to test for novel shared and ancestry-specific AD susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6,728 African American, 8,899 Hispanic (HIS), and 3,232 East Asian individuals, performing within-ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. We identified 13 loci with cross-ancestry associations including known loci at/near CR1 , BIN1 , TREM2 , CD2AP , PTK2B , CLU , SHARPIN , MS4A6A , PICALM , ABCA7 , APOE and two novel loci not previously reported at 11p12 ( LRRC4C ) and 12q24.13 ( LHX5-AS1 ). Reflecting the power of diverse ancestry in GWAS, we observed the SHARPIN locus using 7.1% the sample size of the original discovering single-ancestry GWAS (n=788,989). We additionally identified three GWS ancestry-specific loci at/near ( PTPRK ( P =2.4×10 -8 ) and GRB14 ( P =1.7×10 -8 ) in HIS), and KIAA0825 ( P =2.9×10 -8 in NHW). Pathway analysis implicated multiple amyloid regulation pathways (strongest with P adjusted =1.6×10 -4 ) and the classical complement pathway ( P adjusted =1.3×10 -3 ). Genes at/near our novel loci have known roles in neuronal development ( LRRC4C, LHX5-AS1 , and PTPRK ) and insulin receptor activity regulation ( GRB14 ). These findings provide compelling support for using traditionally-underrepresented populations for gene discovery, even with smaller sample sizes. |
| معلومات مُعتمدة: |
U24 AG021886 United States AG NIA NIH HHS; P30 AG066512 United States AG NIA NIH HHS; U19 AG074879 United States AG NIA NIH HHS; P30 AG066508 United States AG NIA NIH HHS; P30 AG062429 United States AG NIA NIH HHS; P30 AG066462 United States AG NIA NIH HHS; P30 AG066530 United States AG NIA NIH HHS; P30 AG066509 United States AG NIA NIH HHS; P30 AG072977 United States AG NIA NIH HHS; P30 AG062715 United States AG NIA NIH HHS; P30 AG072947 United States AG NIA NIH HHS; P30 AG072972 United States AG NIA NIH HHS; P30 AG072946 United States AG NIA NIH HHS; P30 AG066518 United States AG NIA NIH HHS |
| تواريخ الأحداث: |
Date Created: 20230718 Latest Revision: 20240802 |
| رمز التحديث: |
20240802 |
| مُعرف محوري في PubMed: |
PMC10350126 |
| DOI: |
10.1101/2023.07.06.23292311 |
| PMID: |
37461624 |
| قاعدة البيانات: |
MEDLINE |
