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We investigated the effect of variants in the first three genes in the insulin signaling pathway and genes identified from genome wide association studies (GWAS) of T2D quantitative traits with IR (fasting insulin and the homeostasis model assessment of IR, HOMA-IR) and evaluated gene-environment interactions with IR traits among 1879 nondiabetic middle-aged men from a population-based study conducted in Shanghai, China. One candidate gene, IGF1, was associated with fasting insulin and HOMA-IR. We observed four BMI-gene interactions (P < 0.05) with HOMA-IR (INRS rs7254060, INRS rs7254358, GLU4 rs2113050, and GLU4 rs7713127) and seven BMI-gene interactions with fasting insulin (INRS rs7254060, INRS rs7254358, INRS rs10417205, INRS rs1799817, GLU4 rs12054720 GLU4 rs2113050, and GLU4 rs7713127). There were four WHR-gene interactions with HOMA-IR (INRS rs10417205, INRS rs12971499, INRS rs7254060, and INRS rs7254358), five WHR-gene interactions with fasting insulin (INRS rs10417205, INRS rs7254060, INRS rs7254358, GLU4 rs2113050, and GLU4 rs7713127), eight physical activity-gene interactions with HOMA-IR (INRS rs10411676, INRS rs11671297, INRS rs2229431, INRS rs12461909, INRS rs6510950, INRS rs10420382, IRS2 rs913949, and IRS2 rs2241745) and five physical activity-gene interactions with fasting insulin (INRS rs2229431, INRS rs12461909, INRS rs10420382, IRS2 rs913949, and IRS2 rs2241745). Our results suggest that BMI, WHR and physical activity may modify IR-associated variants., (© 2015 John Wiley & Sons Ltd/University College London.)

Autism is a complex genetic neuropsychiatric condition characterized by deficits in social interaction and language and patterns of repetitive or stereotyped behaviors and restricted interests. Chromosome 15q11.2-q13 is a candidate region for autism susceptibility based on observations of chromosomal duplications in a small percentage of affected individuals and findings of linkage and association. We performed linkage disequilibrium (LD) mapping across a 1-Mb interval containing a cluster of GABA(A) receptor subunit genes (GABRB3, GABRA5, and GABRG3) which are good positional and functional candidates. Intermarker LD was measured for 59 single nucleotide polymorphism (SNP) markers spanning this region, corresponding to an average marker spacing of 17.7 kb(-1). We identified haplotype blocks, and characterized these blocks for common (>5%) haplotypes present in the study population. At this marker resolution, haplotype blocks comprise <50% of the DNA in this region, consistent with a high local recombination rate. Identification of haplotype tag SNPs reduces the overall number of markers necessary to detect all common alleles by only 12%. Individual SNPs and multi-SNP haplotypes were examined for evidence of allelic association to autism, using a dataset of 123 multiplex autism families. Six markers individually, across GABRB3 and GABRA5, and several haplotypes inclusive of those markers, demonstrated nominally significant association. These results are positively correlated with the position of observed linkage. These studies support the existence of one or more autism risk alleles in the GABA(A) receptor subunit cluster on 15q12 and have implications for analysis of LD and association in regions with high local recombination.