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Articles by M Inouye
Total Records ( 2 ) for M Inouye
  D Saleheen , N Soranzo , A Rasheed , H Scharnagl , R Gwilliam , M Alexander , M Inouye , M Zaidi , S Potter , P Haycock , S Bumpstead , S Kaptoge , E Di Angelantonio , N Sarwar , S. E Hunt , N Sheikh , N Shah , M Samuel , S. R Haider , M Murtaza , A Thompson , R Gobin , A Butterworth , U Ahmad , A Hakeem , K. S Zaman , A Kundi , Z Yaqoob , L. A Cheema , N Qamar , A Faruqui , N. H Mallick , M Azhar , A Samad , M Ishaq , S. Z Rasheed , R Jooma , J. H Niazi , A. R Gardezi , N. A Memon , A Ghaffar , F. u Rehman , M. M Hoffmann , W Renner , M. E Kleber , T. B Grammer , J Stephens , A Attwood , K Koch , M Hussain , K Kumar , A Saleem , M. S Daood , A. A Gul , S Abbas , J Zafar , F Shahid , S. M Bhatti , S. S Ali , F Muhammad , G Sagoo , S Bray , R McGinnis , F Dudbridge , B. R Winkelmann , B Boehm , S Thompson , W Ouwehand , W Marz , P Frossard , J Danesh and P. Deloukas

Evidence is sparse about the genetic determinants of major lipids in Pakistanis.

Methods and Results—

Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10–13), APOA5/ZNF259 (rs651821; P<10–13) and GCKR (rs1260326; P<10–13) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10–9). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10–4).


Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.

  I Surakka , K Kristiansson , V Anttila , M Inouye , C Barnes , L Moutsianas , V Salomaa , M Daly , A Palotie , L Peltonen and S. Ripatti

The combining of genome-wide association (GWA) data across populations represents a major challenge for massive global meta-analyses. Genotype imputation using densely genotyped reference samples facilitates the combination of data across different genotyping platforms. HapMap data is typically used as a reference for single nucleotide polymorphism (SNP) imputation and tagging copy number polymorphisms (CNPs). However, the advantage of having population-specific reference panels for founder populations has not been evaluated. We looked at the properties and impact of adding 81 individuals from a founder population to HapMap3 reference data on imputation quality, CNP tagging, and power to detect association in simulations and in an independent cohort of 2138 individuals. The gain in SNP imputation accuracy was highest among low-frequency markers (minor allele frequency [MAF] < 5%), for which adding the population-specific samples to the reference set increased the median R2 between imputed and genotyped SNPs from 0.90 to 0.94. Accuracy also increased in regions with high recombination rates. Similarly, a reference set with population-specific extension facilitated the identification of better tag-SNPs for a subset of CNPs; for 4% of CNPs the R2 between SNP genotypes and CNP intensity in the independent population cohort was at least twice as high as without the extension. We conclude that even a relatively small population-specific reference set yields considerable benefits in SNP imputation, CNP tagging accuracy, and the power to detect associations in founder populations and population isolates in particular.

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