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. 2021 Sep;53(9):1276-1282.
doi: 10.1038/s41588-021-00921-z. Epub 2021 Sep 7.

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Douglas P Wightman  1 Iris E Jansen  1 Jeanne E Savage  1 Alexey A Shadrin  2   3 Shahram Bahrami  2   3   4 Dominic Holland  5 Arvid Rongve  6   7 Sigrid Børte  3   8   9 Bendik S Winsvold  9   10   11 Ole Kristian Drange  12   13 Amy E Martinsen  3   9   10 Anne Heidi Skogholt  9   14 Cristen Willer  15 Geir Bråthen  16   17   18 Ingunn Bosnes  12   19 Jonas Bille Nielsen  9   15   20 Lars G Fritsche  21 Laurent F Thomas  9   14 Linda M Pedersen  10 Maiken E Gabrielsen  9 Marianne Bakke Johnsen  3   8   9 Tore Wergeland Meisingset  16   17 Wei Zhou  22   23 Petroula Proitsi  24 Angela Hodges  24 Richard Dobson  25   26   27   28   29 Latha Velayudhan  24 Karl Heilbron  30 Adam Auton  30 23andMe Research TeamJulia M Sealock  31   32 Lea K Davis  31   32 Nancy L Pedersen  33 Chandra A Reynolds  34 Ida K Karlsson  33   35 Sigurdur Magnusson  36 Hreinn Stefansson  36 Steinunn Thordardottir  37 Palmi V Jonsson  37   38 Jon Snaedal  37 Anna Zettergren  39 Ingmar Skoog  39   40 Silke Kern  39   40 Margda Waern  39   41 Henrik Zetterberg  42   43   44   45 Kaj Blennow  44   45 Eystein Stordal  12   19 Kristian Hveem  9   46 John-Anker Zwart  3   9   10 Lavinia Athanasiu  2   4 Per Selnes  47 Ingvild Saltvedt  16   18 Sigrid B Sando  16   17 Ingun Ulstein  48 Srdjan Djurovic  49   50 Tormod Fladby  3   47 Dag Aarsland  24   51 Geir Selbæk  3   48   52 Stephan Ripke  23   53   54 Kari Stefansson  36 Ole A Andreassen #  2   3   4 Danielle Posthuma #  55   56
Collaborators, Affiliations

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Douglas P Wightman et al. Nat Genet. 2021 Sep.

Erratum in

  • Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease.
    Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, Rongve A, Børte S, Winsvold BS, Drange OK, Martinsen AE, Skogholt AH, Willer C, Bråthen G, Bosnes I, Nielsen JB, Fritsche LG, Thomas LF, Pedersen LM, Gabrielsen ME, Johnsen MB, Meisingset TW, Zhou W, Proitsi P, Hodges A, Dobson R, Velayudhan L, Heilbron K, Auton A; 23andMe Research Team; Sealock JM, Davis LK, Pedersen NL, Reynolds CA, Karlsson IK, Magnusson S, Stefansson H, Thordardottir S, Jonsson PV, Snaedal J, Zettergren A, Skoog I, Kern S, Waern M, Zetterberg H, Blennow K, Stordal E, Hveem K, Zwart JA, Athanasiu L, Selnes P, Saltvedt I, Sando SB, Ulstein I, Djurovic S, Fladby T, Aarsland D, Selbæk G, Ripke S, Stefansson K, Andreassen OA, Posthuma D. Wightman DP, et al. Nat Genet. 2021 Dec;53(12):1722. doi: 10.1038/s41588-021-00977-x. Nat Genet. 2021. PMID: 34773122 No abstract available.
  • Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease.
    Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, Rongve A, Børte S, Winsvold BS, Drange OK, Martinsen AE, Skogholt AH, Willer C, Bråthen G, Bosnes I, Nielsen JB, Fritsche LG, Thomas LF, Pedersen LM, Gabrielsen ME, Johnsen MB, Meisingset TW, Zhou W, Proitsi P, Hodges A, Dobson R, Velayudhan L, Heilbron K, Auton A; 23andMe Research Team; Sealock JM, Davis LK, Pedersen NL, Reynolds CA, Karlsson IK, Magnusson S, Stefansson H, Thordardottir S, Jonsson PV, Snaedal J, Zettergren A, Skoog I, Kern S, Waern M, Zetterberg H, Blennow K, Stordal E, Hveem K, Zwart JA, Athanasiu L, Selnes P, Saltvedt I, Sando SB, Ulstein I, Djurovic S, Fladby T, Aarsland D, Selbæk G, Ripke S, Stefansson K, Andreassen OA, Posthuma D. Wightman DP, et al. Nat Genet. 2022 Jul;54(7):1062. doi: 10.1038/s41588-022-01126-8. Nat Genet. 2022. PMID: 35726068 No abstract available.

Abstract

Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.

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Conflict of interest statement

Competing Interests Statement

All other authors declare no competing interests.

Figures

Figure 1:
Figure 1:
A Manhattan plot of the meta-analysis results highlighting 38 loci, including 7 previously unidentified regions. Only variants with a P< 0.0005 are displayed. The APOE region cannot be fully observed because the y-axis is limited to the top variant in the second most significant locus, -log10(1×10−60), in order to display the less significant variants. The red line represents genome wide significance (5×10−8). The P-values were identified through a meta-analysis (two-sided test) of summary statistics generated by linear/logistic regressions (two-sided test) and were not adjusted for multiple testing. The previously unidentified loci are highlighted in green and indicated by the assigned gene name. The TNIP1/HAVCR2 regions and the NTN5/LILRB2 regions are close enough together that they cannot be visually distinguished at this scale but are different genomic risk loci.

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