PMID- 22243791
OWN - NLM
STAT- MEDLINE
DCOM- 20120306
LR  - 20220311
IS  - 1878-1810 (Electronic)
IS  - 1931-5244 (Print)
IS  - 1878-1810 (Linking)
VI  - 159
IP  - 2
DP  - 2012 Feb
TI  - Molecular genetic studies of complex phenotypes.
PG  - 64-79
LID - 10.1016/j.trsl.2011.08.001 [doi]
AB  - The approach to molecular genetic studies of complex phenotypes evolved 
      considerably during the recent years. The candidate gene approach, which is 
      restricted to an analysis of a few single-nucleotide polymorphisms (SNPs) in a 
      modest number of cases and controls, has been supplanted by the unbiased approach 
      of genome-wide association studies (GWAS), wherein a large number of tagger SNPs 
      are typed in many individuals. GWAS, which are designed on the common 
      disease-common variant hypothesis (CD-CV), identified several SNPs and loci for 
      complex phenotypes. However, the alleles identified through GWAS are typically 
      not causative but rather in linkage disequilibrium (LD) with the true causal 
      variants. The common alleles, which may not capture the uncommon and rare 
      variants, account only for a fraction of heritability of the complex traits. 
      Hence, the focus is being shifted to rare variants-common disease (RV-CD) 
      hypothesis, surmising that rare variants exert large effect sizes on the 
      phenotype. In conjunctional with this conceptual shift, technologic advances in 
      DNA sequencing techniques have dramatically enhanced whole genome or whole exome 
      sequencing capacity. The sequencing approach affords identification of not only 
      the rare but also the common variants. The approach-whether used in 
      complementation with GWAS or as a stand-alone approach-could define the genetic 
      architecture of the complex phenotypes. Robust phenotyping and large-scale 
      sequencing studies are essential to extract the information content of the vast 
      number of DNA sequence variants (DSVs) in the genome. To garner meaningful 
      clinical information and link the genotype to a phenotype, the identification and 
      characterization of a large number of causal fields beyond the information 
      content of DNA sequence variants would be necessary. This review provides an 
      update on the current progress and limitations in identifying DSVs that are 
      associated with phenotypic effects.
CI  - Published by Mosby, Inc.
FAU - Marian, Ali J
AU  - Marian AJ
AD  - Center for Cardiovascular Genetics, Brown Foundation Institute of Molecular 
      Medicine, The University of Texas Health Science Center and Texas Heart 
      Institute, Houston, TX 77030, USA. Ali.J.Marian@uth.tmc.edu
LA  - eng
GR  - R34 HL105563/HL/NHLBI NIH HHS/United States
GR  - R01 HL088498-05/HL/NHLBI NIH HHS/United States
GR  - R21 AG038597/AG/NIA NIH HHS/United States
GR  - R01 HL088498/HL/NHLBI NIH HHS/United States
GR  - R21 AG038597-01/AG/NIA NIH HHS/United States
GR  - R01-088498/PHS HHS/United States
GR  - R21 AG038597-01A1/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110831
PL  - United States
TA  - Transl Res
JT  - Translational research : the journal of laboratory and clinical medicine
JID - 101280339
SB  - IM
CIN - Transl Res. 2012 Feb;159(2):61-3. PMID: 22243790
MH  - Alleles
MH  - Base Sequence/*genetics
MH  - Case-Control Studies
MH  - Databases, Genetic
MH  - Exome/*genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - Genetic Variation/*genetics
MH  - Genome, Human/*genetics
MH  - Genome-Wide Association Study/*methods
MH  - Genotype
MH  - Humans
MH  - Linkage Disequilibrium/genetics
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide/genetics
MH  - *Sequence Analysis, DNA/methods/trends
PMC - PMC3259530
MID - NIHMS346353
COIS- Conflict of Interest: There is no conflict of interest to declare. The author 
      have read the journal's policy on disclosure of potential conflicts of interes
EDAT- 2012/01/17 06:00
MHDA- 2012/03/07 06:00
PMCR- 2013/02/01
CRDT- 2012/01/17 06:00
PHST- 2011/06/03 00:00 [received]
PHST- 2011/08/03 00:00 [revised]
PHST- 2011/08/04 00:00 [accepted]
PHST- 2012/01/17 06:00 [entrez]
PHST- 2012/01/17 06:00 [pubmed]
PHST- 2012/03/07 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - S1931-5244(11)00261-1 [pii]
AID - 10.1016/j.trsl.2011.08.001 [doi]
PST - ppublish
SO  - Transl Res. 2012 Feb;159(2):64-79. doi: 10.1016/j.trsl.2011.08.001. Epub 2011 Aug 
      31.