Decision letter for "Genetic risk score modifies the effect of <i>APOE</i> on risk and age onset of Alzheimer's disease"

AbstractObjectivesWeight loss is common in the years before an Alzheimer’s disease (AD) diagnosis, likely due to changes in appetite and diet. The age at which this change in body mass index (BMI) emerges is unclear but may point to the earliest manifestations of AD, timing that may be important for identifying windows of intervention or risk reduction. We examined the association between AD genetic risk and cross-sectional BMI across adults in mid-to late-life as an innovative approach to determine the age at which BMI changes and may indicate preclinical AD.DesignObservational studySettingUK BiobankParticipants407,386 UK Biobank non-demented participants aged 39-70 with Caucasian genetic ancestry enrolled 2007-2010.Main Outcome MeasuresBMI (kg/m2) was constructed from height and weight measured during the initial visit. A genetic risk score for AD (AD-GRS) was calculated as a weighted sum of 23 genetic variants previously confirmed to be genome-wide significant predictors of AD (Z-scored). We evaluated whether the association of AD-GRS with BMI differed by age using linear regression with adjustment for sex and genetic ancestry, stratified by age grouping (40-60, 61+). We calculated the earliest age at which high AD-GRS predicted divergence in BMI compared to normal age-related BMI trends with linear and quadratic terms for age and interactions with AD-GRS.ResultsIn 39-49 year olds, AD-GRS was not significantly associated with lower BMI (0.00 kg/m2 per SD in AD-GRS; 95%CI: -0.03,0.03). In 50-59 year olds AD-GRS was associated with lower BMI (-0.03 kg/m2 per 1 SD in AD-GRS; 95%CI:-0.06,-0.01) and this association was stronger in 60-70 year olds (-0.09 kg/m2 per 1 SD in AD-GRS; 95%CI:-0.12,-0.07). Model-based BMI age-curves for people with high versus low AD-GRS scores began to diverge after age 47.InterpretationGenetic factors that increase AD risk begin to predict lower BMI in adults by age 50, with greater effect later in older ages. Weight loss may manifest as an early pathophysiologic change associated with AD.

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Evaluation of a Genetic Risk Score to Improve Risk Prediction for Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-150749 ◽

2016 ◽

Vol 53 (3) ◽

pp. 921-932 ◽

Cited By ~ 45

Author(s):

Vincent Chouraki ◽

Christiane Reitz ◽

Fleur Maury ◽

Joshua C. Bis ◽

Celine Bellenguez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Prediction ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score

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[P1-139]: PATHWAY-SPECIFIC GENETIC RISK SCORE ASSOCIATED WITH ALZHEIMER's DISEASE AND WHITE MATTER LESIONS IN COGNITIVELY NORMAL SUBJECTS

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.06.206 ◽

2017 ◽

Vol 13 (7S_Part_6) ◽

pp. P295-P296

Author(s):

Shahzad Ahmad ◽

Christian Bannister ◽

Sven J. van der Lee ◽

Dina Vojinovic ◽

Hieab H.H. Adams ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

White Matter Lesions ◽

Normal Subjects ◽

Cognitively Normal ◽

Cognitively Normal Subjects

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The Interplay of Diet Quality and Alzheimer’s Disease Genetic Risk Score in Relation to Cognitive Performance Among Urban African Americans

Nutrients ◽

10.3390/nu11092181 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2181 ◽

Cited By ~ 2

Author(s):

Sharmin Hossain ◽

May A. Beydoun ◽

Marie F Kuczmarski ◽

Salman Tajuddin ◽

Michele K Evans ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Performance ◽

Risk Score ◽

Diet Quality ◽

Genetic Risk ◽

Verbal Fluency ◽

Genetic Risk Score ◽

Healthy Eating Index ◽

Cognitive Test

We examined the interactive associations of poor diet quality and Alzheimer’s Disease (AD) genetic risk with cognitive performance among 304 African American adults (mean age~57 years) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. In this cross-sectional study, selected participants had complete predictors and covariate data with 13 cognitive test scores as outcomes. Healthy Eating Index-2010 (HEI-2010), Dietary Approaches to Stop Hypertension (DASH), and mean adequacy ratio (MAR) were measured. A genetic risk score for AD in HANDLS (hAlzScore) was computed from 12 selected single nucleotide polymorphisms (SNPs). Our key hypotheses were tested using linear regression models. The hAlzScore was directly associated with poor performance in verbal memory (−0.4 ± 0.2, 0.01) and immediate visual memory (0.4 ± 0.2, 0.03) measured in seconds, in women only. The hAlzScore interacted synergistically with poorer diet quality to determine lower cognitive performance on a test of verbal fluency. Among numerous SNP × diet quality interactions for models of cognitive performance as outcomes, only one passed correction for multiple testing, namely verbal fluency. Our results suggest that improved diet quality can potentially modify performance on cognitive tests of verbal fluency among individuals with higher AD genetic risk.

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