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Articles by F Dudbridge
Total Records ( 2 ) for F Dudbridge
  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
  Background—

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).

Conclusions—

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. M Goodyer , T Croudace , F Dudbridge , M Ban and J. Herbert
 

Background

There is increasing evidence for genetic effects on the hypothalamic–pituitary axis system. More than one gene is likely to moderate corticoid-mediated activity.

Aims

To investigate whether the brain-derived neurotrophic factor (BDNF) polymorphism (rs6265, Val66Met) is associated with morning waking salivary cortisol and moderates the corticoid-mediated risk for subsequent depressive episode onset independently of the known effects of 5-HTTLPR (the serotonin transporter gene promoter).

Method

High-risk adolescents (n = 401) were genotyped for Val66Met BDNF and 5-HTTLPR. Salivary samples were obtained on four consecutive school days within 1 h of waking. There were 365 (91%) remaining participants reassessed at 12 months for episodes of psychiatric disorder in the follow-up period. Of these, 357 (89%) had complete data for multivariate modelling.

Results

There were 41 (11.2%) individuals who reported a new episode of clinical depression over the follow-up period. Increased risk for subsequent depression was found in carriers of the Val66Val genotype in BDNF with higher morning waking cortisol. This remained present when the known interaction between carriers of a short allele of 5-HTTLPR with higher morning salivary cortisol was taken into account.

Conclusions

Both BDNF and 5-HTTLPR genes show evidence of modifying the risk of a subsequent new depressive episode associated with elevated morning salivary cortisol. In adolescents morning salivary cortisol levels may constitute a biomarker for some forms of unipolar depression.

 
 
 
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