Es between cases and controls, shared heterozygosity among cases was checked, allelic association was analyzed by using Haploview, and haplotype association was analyzed by both Haploview and Haplotype Pattern Mining [24,25].Candidate Gene AnalysesAltogether five candidate genes in the 9q34 linkage peak were chosen based on their biological relevance in immunity or infections (Table 2). After PCR with flanking intronic primers, all exons were sequenced 18325633 in index individuals from the six families (11, 12, 13, 28, 40, and 46) showing most significant linkage (Table S1). Similarly, exons and exon-intron boundaries of AGTR1 (Angiotensin II receptor, type 1) were sequenced in six probands from the families (7, 13, 37, 40, 43, and 46) showing linkage to the 3q22 area. All PCR reactions were performed in 5 ml volumes containing 20 ng of DNA, with standard reagent concentrations and temperature profiles. BI 10773 Sequencing was performed using dyeterminator chemistry and automated sequencers (ABI, Columbia, Maryland, United States). Primer sequences are available on request.HMA10K Array (Table 3, Figure 2). The Empagliflozin strongest linkage was on chromosome 9q34 (rs578802- rs708616), with an NPLall score of 3.84 and a suggestive genome-wide p-value of 0.24. Results were identical when the analysis was repeated with Caucasian allele frequency estimates from Affymetrix, except that the chromosome 3 peak marker moved from 3p24 (rs1994987) to 3p22 (rs2167176) with an NPLall score of 2.64 and a genome-wide P-value 0.94. Generally, different families contributed strongest to the most significant peaks: 9q34 (Families 12 NPLall 3.2 and 13 NPLall 4.8); 3q22-q24 (Families 13 NPLall.5 and 37 NPLall 2.0); 21q22 (Families 12 NPLall 3.7 and 21 NPLall 2.5); and 22q13 (Families 12 
NPLall 2.0 and 31 NPLall 1.7).Verification of Linkage PeaksGenotyping 91 affected and non-affected individuals from 19 families with 31 microsatellite markers surrounding the four most suggestive linkage peaks on 3q22-24, 9q34, 21q22, and 22q13 revealed one significant linkage peak for 9q34 with the highest NPLall of 2.77 and p = 0.026 for D9S159 (minimum NPLall score for significant linkage was 2.49) 23727046 (Table 1). Only suggestive linkage was seen for 3q22-24, 21q22, and 22q13 (Table 1). The highest NPLall score was at 9q34 in both configurations. Families 12 and 13 contributed again strongest to the linkage peak on chromosome 9q34, with the highest NPLall scores of 3.64 at D9S179 and 5.02 at D9S313, respectively, and four other families showed suggestive linkage (NPLall scores of 1.34?.41) (Table S1).Results Initial Non-parametric Genome-wide Linkage ResultsWe found seven suggestive linkage peaks on chromosomes 9q34, 3q22-24, 21q22, 22q13, 3p24, 10q25, and 11q24, in descending order of genomic significance, on the AffymetrixTable 1. Non-parametric linkage results from using additional microsatellite markers surrounding the suggested linkage peaks.Chromosomal locus NPLall Genome-wide p-value 0.692 0.660 0.703 0.708 0.762 0.761 0.651 0.629 0.669 0.732 0.803 0.921 0.959 0.074 0.026 0.034 0.035 0.063 0.104 0.560 0.491 0.482 0.497 0.723 0.914 0.933 0.51 0.37 0.84 0.29 0.22 0.889 0.938 0.766 0.959 0.967 0.00 2.26 2.71 2.62 2.60 2.36 2.14 1.34 1.47 1.48 1.46 1.01 0.49 0.48 0.66 0.52 0.98 0.38 0.29 0.33 0.52 0.45 0.69 1.19 0.75 (3.93) 0.79 0.77 0.32 0.65 (2.53) 0.84 1.08 0.39 1.20 0.74 (4.25) 0.14 0.46 0.61 0.72 0.94 1.01 1.38 0.84 3.19 2.75 3.62 (26.66) 1.04 2.47 0.96 1.96 0.94 1.18 1.04 1.46 1.05 3.31 1.16 3.50.Es between cases and controls, shared heterozygosity among cases was checked, allelic association was analyzed by using Haploview, and haplotype association was 
analyzed by both Haploview and Haplotype Pattern Mining [24,25].Candidate Gene AnalysesAltogether five candidate genes in the 9q34 linkage peak were chosen based on their biological relevance in immunity or infections (Table 2). After PCR with flanking intronic primers, all exons were sequenced 18325633 in index individuals from the six families (11, 12, 13, 28, 40, and 46) showing most significant linkage (Table S1). Similarly, exons and exon-intron boundaries of AGTR1 (Angiotensin II receptor, type 1) were sequenced in six probands from the families (7, 13, 37, 40, 43, and 46) showing linkage to the 3q22 area. All PCR reactions were performed in 5 ml volumes containing 20 ng of DNA, with standard reagent concentrations and temperature profiles. Sequencing was performed using dyeterminator chemistry and automated sequencers (ABI, Columbia, Maryland, United States). Primer sequences are available on request.HMA10K Array (Table 3, Figure 2). The strongest linkage was on chromosome 9q34 (rs578802- rs708616), with an NPLall score of 3.84 and a suggestive genome-wide p-value of 0.24. Results were identical when the analysis was repeated with Caucasian allele frequency estimates from Affymetrix, except that the chromosome 3 peak marker moved from 3p24 (rs1994987) to 3p22 (rs2167176) with an NPLall score of 2.64 and a genome-wide P-value 0.94. Generally, different families contributed strongest to the most significant peaks: 9q34 (Families 12 NPLall 3.2 and 13 NPLall 4.8); 3q22-q24 (Families 13 NPLall.5 and 37 NPLall 2.0); 21q22 (Families 12 NPLall 3.7 and 21 NPLall 2.5); and 22q13 (Families 12 NPLall 2.0 and 31 NPLall 1.7).Verification of Linkage PeaksGenotyping 91 affected and non-affected individuals from 19 families with 31 microsatellite markers surrounding the four most suggestive linkage peaks on 3q22-24, 9q34, 21q22, and 22q13 revealed one significant linkage peak for 9q34 with the highest NPLall of 2.77 and p = 0.026 for D9S159 (minimum NPLall score for significant linkage was 2.49) 23727046 (Table 1). Only suggestive linkage was seen for 3q22-24, 21q22, and 22q13 (Table 1). The highest NPLall score was at 9q34 in both configurations. Families 12 and 13 contributed again strongest to the linkage peak on chromosome 9q34, with the highest NPLall scores of 3.64 at D9S179 and 5.02 at D9S313, respectively, and four other families showed suggestive linkage (NPLall scores of 1.34?.41) (Table S1).Results Initial Non-parametric Genome-wide Linkage ResultsWe found seven suggestive linkage peaks on chromosomes 9q34, 3q22-24, 21q22, 22q13, 3p24, 10q25, and 11q24, in descending order of genomic significance, on the AffymetrixTable 1. Non-parametric linkage results from using additional microsatellite markers surrounding the suggested linkage peaks.Chromosomal locus NPLall Genome-wide p-value 0.692 0.660 0.703 0.708 0.762 0.761 0.651 0.629 0.669 0.732 0.803 0.921 0.959 0.074 0.026 0.034 0.035 0.063 0.104 0.560 0.491 0.482 0.497 0.723 0.914 0.933 0.51 0.37 0.84 0.29 0.22 0.889 0.938 0.766 0.959 0.967 0.00 2.26 2.71 2.62 2.60 2.36 2.14 1.34 1.47 1.48 1.46 1.01 0.49 0.48 0.66 0.52 0.98 0.38 0.29 0.33 0.52 0.45 0.69 1.19 0.75 (3.93) 0.79 0.77 0.32 0.65 (2.53) 0.84 1.08 0.39 1.20 0.74 (4.25) 0.14 0.46 0.61 0.72 0.94 1.01 1.38 0.84 3.19 2.75 3.62 (26.66) 1.04 2.47 0.96 1.96 0.94 1.18 1.04 1.46 1.05 3.31 1.16 3.50.
