Segmentation scores at <i>FCGR3A</i> and <i>FCGR3B</i> derived from DNAcopy (23).

<p>Segmentation scores at <i>FCGR3A</i> and <i>FCGR3B</i> derived from DNAcopy (23).</p

Concordance of the three methods: Hollox et al.

<p>(14), CNVnator and CNVrd. 0/1 is deletion, 2 is CN = 2 and 3/4 is duplication.</p

CNVrd, a Read-Depth Algorithm for Assigning Copy-Number at the FCGR Locus: Population-Specific Tagging of Copy Number Variation at <i>FCGR3B</i>

<div><p>The extent of contribution from common gene copy number (CN) variants in human disease is currently unresolved. Part of the reason for this is the technical difficulty in directly measuring CN variation (CNV) using molecular methods, and the lack of single nucleotide polymorphisms (SNPs) that can tag complex CNV that has arisen multiple times on different SNP haplotypes. One CNV locus implicated in human disease is <i>FCGR</i>. Here we aimed to use next-generation sequencing (NGS) data from the 1000 Genomes Project to assign CN at <i>FCGR3A</i> and <i>FCGR3B</i> and to comprehensively assess the ability of SNPs to tag specific CN variants. A read-depth algorithm was developed (CNVrd) and validated on a subset of HapMap samples using CN assignments that had previously been determined using molecular and microarray methods. At 7 out of 9 other complex loci there was >90% concordance with microarray data. However, given that some prior knowledge of CN is required, the generalizability of CNVrd is limited and should be applied to other complex CNV loci with caution. Subsequently, CN was assigned et <i>FCGR3B</i> using CNVrd in a total of 952 samples from the 1000 Genomes Project, using three classes and SNPs that correlated with duplication were identified. The best tag SNP was observed in the Mexican-American sample set for duplication at <i>FCGR3B</i>. This SNP (rs117435514, r² = 0.79) also tagged similar duplication in Chinese and Japanese (r² = 0.35–0.60), but not in Caucasian or African. No tag SNP for duplication at <i>FCGR3A</i> or deletion at <i>FCGR3B</i> was identified in any population. We conclude that it is possible to tag CNV at the FCGR locus, but CN and SNPs have to be characterized and correlated on a population-specific basis.</p></div

Characteristics of heavy SSB consumers.

<p>* Exercise category was defined as 1 for sedentary, 2 for moderately active, 3 for regular strenuous exercise and 4 for regular hard physical training.</p><p>Characteristics of heavy SSB consumers.</p

Analysis of association of <i>PTPN22</i> ‘haplotype 5’ (<i>rs3789607</i>: T&gt;C) with rheumatoid arthritis.

<p>1 Cases top line, controls bottom line. The Carlton Set 2 cases and controls, the combined other cases and total cases deviated mildly from HWE (<i>P</i> = 0.02, 0.03, 0.05 and 0.02, respectively).</p><p>2 Allele 2; number of chromosomes (frequency).</p><p>3 Genotype data from <i>rs17274634</i> were used (r² = 1 with <i>rs3789607</i> in CEPH CEU (<a href="http://www.hapmap.org" target="_blank">www.hapmap.org</a>)).</p><p>4 The Mantel-Haenszel pooled OR = 0.87 [0.82–0.93], <i>P</i> = 7.5×10⁻⁶; Breslow-Day test for heterogeneity <i>P</i> = 0.083. The Mantel-Haenszel pooled OR excluding Carlton et al data was 0.91 [0.85–0.98], <i>P</i> = 0.016; Breslow-Day <i>P</i> = 0.50.</p

<i>Rs2476601-rs12566340</i> haplotypic analysis.

<p>1. Within each cell in the RA half, NZ data are top, WTCCC data middle and combined bottom.</p

<i>Rs2149356</i> genotype and association with risk of gout in the HPFS and NHS sample sets.

<p><i>Rs2149356</i> genotype and association with risk of gout in the HPFS and NHS sample sets.</p