Relationship between <i>DNMT</i> variants and standardised¹ Moray House Test (MHT) score.

1<p>Transformed to normalised IQ type scale of mean 100 and standard deviation 15.</p>2<p>TT>CT>CC.</p>3<p>CT/TT>CC.</p

Kernel density plots of childhood Moray House test score in childhood (age 11yrs - - - -) and adulthood (age 70yrs ——) Moray House Test score.

<p>Kernel density plots of childhood Moray House test score in childhood (age 11yrs - - - -) and adulthood (age 70yrs ——) Moray House Test score.</p

Heat map of associations between the polygenic profile scores for neurodegenerative disease and cognitive ability and physical health.

<p>Stronger associations are indicated by darker shades, red indicates a positive association, blue indicates a negative association. AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; TMT B-A, trail-making part B–part A; TMT B, trail making part B; TMT A, trail making part A; DSS, digit symbol substitution; VNR, verbal numerical reasoning; FVC, forced vital capacity; PEF, peak expiratory flow; FEV1, forced expiratory volume in 1s. *, significant association after FDR correction (p-value ≤ 0.018 (AD), 0.024 (ALS), or 0.0041 (FTD)). Full results can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198187#pone.0198187.s001" target="_blank">S1 Table</a>.</p

Associations between polygenic risk scores for Alzheimer’s disease (FDR p-value ≤ 0.018), amyotrophic lateral sclerosis (FDR p-value ≤ 0.0024), and frontotemporal dementia (FDR p-value ≤ 0.0041), and cognitive and physical measures controlling for age, sex, assessment centre, genotyping batch and array and 10 genetic principal components for population structure.

<p>Associations between polygenic risk scores for Alzheimer’s disease (FDR p-value ≤ 0.018), amyotrophic lateral sclerosis (FDR p-value ≤ 0.0024), and frontotemporal dementia (FDR p-value ≤ 0.0041), and cognitive and physical measures controlling for age, sex, assessment centre, genotyping batch and array and 10 genetic principal components for population structure.</p

<i>DNMT3L</i> 11330C>T genotype frequencies – CC and T allele carriers (CT/TT) – by MHT score tertile.

<p><i>DNMT3L</i> 11330C>T genotype frequencies – CC and T allele carriers (CT/TT) – by MHT score tertile.</p

Cognitive and physical variable comparison between high Alzheimer’s disease (AD) polygenic risk, amyotrophic lateral sclerosis (ALS) polygenic risk, and frontotemporal dementia (FTD) polygenic risk, N for each group is shown.

<p>Cognitive and physical variable comparison between high Alzheimer’s disease (AD) polygenic risk, amyotrophic lateral sclerosis (ALS) polygenic risk, and frontotemporal dementia (FTD) polygenic risk, N for each group is shown.</p

<i>DNMT3L</i> 11330 genotype and risk of being in the lowest Moray House Test score centile.

1<p><i>DNMT3L</i> 11330 CC>CT>TT.</p>2<p><i>DNMT3L</i> 11330 CC>CT/TT.</p

<i>DNMT</i> variant genotype and allele frequencies in ABC1936 and LBC1936.

<p>Genotype counts are presented with percentages in brackets.</p

Top 20 independent autosomal GWAS hits.

<p>Top 20 independent autosomal GWAS hits.</p

Population-sense regional heritability for each brain-measured intermediate phenotype within the top g_f associated region on chromosome 5.

<p>²_ps: estimated regional population-sense heritability, SE: estimated standard error of the regional population-sense heritability. P:p-value from the LRT test testing the significance of the genetic variance component. Tissue: brain region, h</p