Demographics of Amish Samples Used For Follow-up Genotyping.

<p>Percent female, age of exam and onset averages and standard deviations were calculated for the 921 samples which passed QC for follow-up genotyping.</p><p>Demographics of Amish Samples Used For Follow-up Genotyping.</p

MQLS-corrected allele frequencies and case-control association p-values for the top sequencing variants in the sequencing dataset.

<p>Chr = chromosome. MAF = minor allele frequency. Nucleotide position is based upon the UCSC hg19 human reference genome. Gene and Function annotated by SeattleSeq134.</p><p>MQLS-corrected allele frequencies and case-control association p-values for the top sequencing variants in the sequencing dataset.</p

Details of Risk Loci from Meta-Analysis Used to Calculate Total Genetic Risk Score.

<p>Alleles, MAF, and overall OR are published values. Chr = chromosome. Pos = position in bp. MAF = minor allele frequency. OR = odds ratio. Adapted from Lambert, et al, 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118043#pone.0118043.ref016" target="_blank">16</a>]. Allele frequency was calculated using the 921 Amish samples and the 971 samples from the unrelated dataset that passed QC in the follow-up genotyping phase.</p><p>Details of Risk Loci from Meta-Analysis Used to Calculate Total Genetic Risk Score.</p

Distributions of Total Genetic Risk Scores.

<p>Total genetic risk score averages and standard deviations were calculated for the 629 Amish LOAD cases and cognitively normal controls and the 971 LOAD cases and cognitively normal controls from the unrelated case-control dataset who passed QC for the follow-up genotyping phase. n = total number of individuals. μ = average total risk score for group.</p

Flow Diagram of this Study.

<p>Individuals were selected from the full Amish dataset for whole-exome sequencing. The variants identified from these data were used to screen three classes of variants, genes that are very near or contain GWAS hits or carry early-onset mutations, genes within four candidate linkage regions implicated by previous studies and genes that harbor variants that occur uniquely in cases or in controls. The top variants from these three classes were then genotyped in the full dataset and case-control association was performed.</p

Demographics of Amish Exome Sequencing Samples.

<p>Percent female, age of exam and onset averages and standard deviations were calculated for the 162 samples which passed QC for whole-exome sequencing.</p><p>Demographics of Amish Exome Sequencing Samples.</p

Demographics of Genetic Risk Score Samples.

<p>Percent female, age of exam and onset averages and standard deviations were calculated for 629 Amish samples and the 971 samples from the unrelated dataset which passed QC for follow-up genotyping.</p><p>Demographics of Genetic Risk Score Samples.</p

MQLS-corrected allele frequencies and case-control association p-values for the top variants in the full dataset.

<p>Chr = chromosome. MAF = minor allele frequency. Nucleotide position is based upon the UCSC hg19 human reference genome. Gene annotated by SeattleSeq134.</p><p>* Variant in implicated linkage regions.</p><p>+ Variant in implicated AD gene.</p><p>MQLS-corrected allele frequencies and case-control association p-values for the top variants in the full dataset.</p

Summary of Variant QC from the Follow-up Genotyping.

<p>Sequence variant = variant identified from whole-exome sequence data. GWAS hit = SNP implicated by two recent meta-analyses [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118043#pone.0118043.ref016" target="_blank">16</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118043#pone.0118043.ref018" target="_blank">18</a>]. Complete dataset = all variants and markers genotyped in three Sequenom pools and two TaqMan assays.</p><p>Summary of Variant QC from the Follow-up Genotyping.</p

Percentage of SNPs (type 1 error) above parametric HLOD and nonparametric LOD thresholds using PedCut followed by multipoint parametric linkage analyses assuming dominant and recessive models and nonparametric linkage analysis using the ‘all’ and ‘pairs’ statistics.

<p>Percentage of SNPs (type 1 error) above parametric HLOD and nonparametric LOD thresholds using PedCut followed by multipoint parametric linkage analyses assuming dominant and recessive models and nonparametric linkage analysis using the ‘all’ and ‘pairs’ statistics.</p