Family-based association results between DN-associated SNPs and nephropathy (normoalbuminuria vs. high microalbuminuria/proteinuria/ESRD) among diabetic family members.

#<p>Families  =  number of nuclear families informative for the FBAT analysis.</p><p>S-E(S)  =  observed minus the expected transmission for each allele.</p><p>Var(S)  =  variance of the observed transmission for each allele.</p><p>Z score: positive values indicate risk alleles (i.e., increased transmission to affected individuals), negative values indicate protective alleles (i.e., reduced transmission to affected individuals).</p><p>Associations achieving nominal significance (<i>P</i>-value<0.05) are indicated in bold.</p>*<p>Risk allele reported in <i>Pezzolesi et al</i>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060301#pone.0060301-Pezzolesi2" target="_blank">[18]</a></p

Family-based association results between DN-associated SNPs and advanced nephropathy (normoalbuminuria vs. proteinuria/ESRD) among diabetic family members.

#<p>Families  =  number of nuclear families informative for the FBAT analysis.</p><p>S-E(S)  =  observed minus the expected transmission for each allele.</p><p>Var(S)  =  variance of the observed transmission for each allele.</p><p>Z score: positive values indicate risk alleles (i.e., increased transmission to affected individuals), negative values indicate protective alleles (i.e., reduced transmission to affected individuals).</p>*<p>Risk allele reported in <i>Pezzolesi et al</i>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060301#pone.0060301-Pezzolesi2" target="_blank">[18]</a></p

Clinical characteristics of 798 examined members from 66 families from the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes Family Collection.

<p>Baseline clinical characteristics are presented as mean values ± standard deviation.</p><p>HbA_1c, glycosylated hemoglobin. ESRD, end-stage renal disease.</p>*<p>ESRD patients were assigned ACR values of 3500 µg/mg.</p>†<p>High microalbuminuria was defined as an ACR between 100 and 300 µg/mg.</p>‡<p>ESRD status was updated for members of this collection through the United States Renal Data System as of August 2008.</p

Family-based haplotype analysis between chromosome 9q21.32^* haplotypes and advanced nephropathy (normoalbuminuria vs. proteinuria/ESRD) and nephropathy (normoalbuminuria vs. high microalbuminuria/proteinuria/ESRD) among diabetic family members.

*<p>9q21.32 haplotypes: rs1888747, rs1929547, and rs10868025.</p><p>Haplotypes with estimated frequencies ≥0.01 are provided and were used to calculate global <i>P</i>-values.</p>#<p>Families  =  number of nuclear families informative for the HBAT analysis; a minimum of 5 informative families for each haplotype was required to compute global tests.</p><p>S-E(S)  =  observed minus the expected transmission for each haplotype.</p><p>Var(S)  =  variance of the observed transmission for each haplotype.</p><p>Z score: positive values indicate risk haplotypes, negative values indicate protective haplotypes.</p><p>Associations achieving nominal significance (<i>P</i>-value<0.05) are indicated in bold.</p

Family-based association analysis between DN-associated SNPs and logACR among diabetic family members.

<p># Families  =  number of nuclear families informative for the FBAT analysis.</p><p>S-E(S)  =  observed minus the expected transmission for each allele.</p><p>Var(S)  =  variance of the observed transmission for each allele.</p><p>Z score: positive values indicate risk alleles, negative values indicate protective alleles.</p>*<p>Risk allele reported in <i>Pezzolesi et al</i>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060301#pone.0060301-Pezzolesi2" target="_blank">[18]</a></p

Family-based association results between DN-associated SNPs and ESRD among diabetic family members.

#<p>Families  =  number of nuclear families informative for the FBAT analysis.</p><p>S-E(S)  =  observed minus the expected transmission for each allele.</p><p>Var(S)  =  variance of the observed transmission for each allele.</p><p>Z score: positive values indicate risk alleles (i.e., increased transmission to affected individuals), negative values indicate protective alleles (i.e., reduced transmission to affected individuals).</p>*<p>Risk allele reported in <i>Pezzolesi et al</i>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060301#pone.0060301-Pezzolesi2" target="_blank">[18]</a></p

Summary of the relative pairs in the 66 families from the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes Family Collection according to diabetes and nephropathy status.

<p>Advanced DN  =  diabetic individuals with proteinuria or ESRD; DN  =  diabetic individuals with high microalbuminuria, proteinuria, or ESRD.</p

Family-based haplotype analysis between chromosome 9q21.32^* haplotypes and logACR among diabetic family members.

*<p>9q21.32 haplotypes: rs1888747, rs1929547, and rs10868025.</p><p>Haplotypes with estimated frequencies ≥0.01 are provided and were used to calculate global <i>P</i>-values.</p>#<p>Families  =  number of nuclear families informative for the HBAT analysis; a minimum of 5 informative families for each haplotype was required to compute global tests.</p><p>S-E(S)  =  observed minus the expected transmission for each haplotype.</p><p>Var(S)  =  variance of the observed transmission for each haplotype.</p><p>Z score: positive values indicate risk haplotypes, negative values indicate protective haplotypes.</p><p>Associations achieving nominal significance (<i>P</i>-value<0.05) are indicated in bold.</p

Top GWAS associations, by ethnicity.

<p>¹ P-values shown are additive unless another model is denoted next to the p-value (d = dominant model, r = recessive model). RA is risk allele. The odds ratio (OR) is presented for the risk allele, compared with the non-risk allele, for a given model. Direction (discovery) is read in the order: AA-AI-EA-MA; Direction (replication) is read in the order: AA-AI-EA; a “?” denotes that ethnicity’s data did not pass QC and was not included in the meta-analysis. A “+” or “-”indicates the direction of the effect in individuals of a specific ancestry.</p><p>Top GWAS associations, by ethnicity.</p

Demographic characteristics of study populations.

<p><b>† In the African American sample, we obtained out-of-study samples from Wake Forest University and Howard University (see</b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005352#sec009" target="_blank">Methods</a><b>). Their demographic characteristics are as follows: 931 DKD cases are 60.3% female, Age in years 61.6 ± 10.5, DM duration in years 19.7 ± 10.7; 92 Diabetic controls are all female, Age in years 55.1 ± 11.6, No Diabetes duration available; 1288 Non-Diabetic controls are 35.5% female, Age in years 48.0 ± 12.4. FILR–FIND Large Replication study.</b></p><p>Demographic characteristics of study populations.</p