Instruct: Identify the main category of Medrxiv papers based on the titles and abstracts
Query: A novel age-informed approach for genetic association analysis in Alzheimer's disease IntroductionMany Alzheimers disease (AD) genetic association studies disregard age or incorrectly account for it, hampering variant discovery.

MethodUsing simulated data, we compared the statistical power of several models: logistic regression on AD diagnosis adjusted and not adjusted for age; linear regression on a score integrating case-control status and age; and multivariate Cox regression on age-at-onset. We applied these models to real exome-wide data of 11,127 sequenced individuals (54% cases) and replicated suggestive associations in 21,631 genotype-imputed individuals (51% cases).

ResultsModelling variable AD risk across age results in 10-20% statistical power gain compared to logistic regression without age adjustment, while incorrect age adjustment leads to critical power loss. Applying our novel AD-age score and/or Cox regression, we discovered and replicated novel variants associated with AD on KIF21B, USH2A, RAB10, RIN3 and TAOK2 genes.

DiscussionOur AD-age score provides a simple means for statistical power gain and is recommended for future AD studies.
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The categories of this paper are: rehabilitation
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The categories of this paper are: research
25
The categories of this paper are: improvement
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The categories of this paper are: primary
42
The categories of this paper are: occupational
1
The categories of this paper are: sports
51
The categories of this paper are: education
22
The categories of this paper are: clinical
37
The categories of this paper are: aids
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The categories of this paper are: environmental
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The categories of this paper are: gastroenterology
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The categories of this paper are: reproductive
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The categories of this paper are: urology
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The categories of this paper are: global
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The categories of this paper are: nutrition
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The categories of this paper are: pediatrics