Meta-analysis of genetic association with diagnosed Alzheimer’s disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing
Introduction Late-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly1, and risk is partially driven by genetics2. Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS)3–8. To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci (IQCK, ACE, ADAM10, and ADAMTS1). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7) indicating that additional rare variants remain to be identified..
| Medienart: |
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Preprint| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
bioRxiv.org - (2019) vom: 19. Juli Zur Gesamtaufnahme - year:2019 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kunkle, BW [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/294629 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
XBI017903548 |
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| 100 | 1 | |a Kunkle, BW |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Meta-analysis of genetic association with diagnosed Alzheimer’s disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Introduction Late-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly1, and risk is partially driven by genetics2. Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS)3–8. To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci (IQCK, ACE, ADAM10, and ADAMTS1). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7) indicating that additional rare variants remain to be identified. | ||
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| 700 | 1 | |a Leverenz, JB |e verfasserin |4 aut | |
| 700 | 1 | |a Mann, D |e verfasserin |4 aut | |
| 700 | 1 | |a Levey, AI |e verfasserin |4 aut | |
| 700 | 1 | |a Pickering-Brown, S |e verfasserin |4 aut | |
| 700 | 1 | |a Lieberman, AP |e verfasserin |4 aut | |
| 700 | 1 | |a Klopp, N |e verfasserin |4 aut | |
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| 700 | 1 | |a Marson, DC |e verfasserin |4 aut | |
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| 700 | 1 | |a Mash, DC |e verfasserin |4 aut | |
| 700 | 1 | |a Nöthen, MM |e verfasserin |4 aut | |
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| 700 | 1 | |a Hooper, NM |e verfasserin |4 aut | |
| 700 | 1 | |a McCormick, WC |e verfasserin |4 aut | |
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| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2019) vom: 19. Juli |
| 773 | 1 | 8 | |g year:2019 |g day:19 |g month:07 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/294629 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2019 |b 19 |c 07 | ||
| 953 | |2 045F |a 570 | ||